Publications by authors named "Francesco Cavani"

34 Publications

Identification of Sclerostin as a Putative New Myokine Involved in the Muscle-to-Bone Crosstalk.

Biomedicines 2021 Jan 12;9(1). Epub 2021 Jan 12.

Department of Biomedical, Metabolic and Neural Sciences, Section of Human Morphology, University of Modena and Reggio Emilia, 41124 Modena, Italy.

Bone and muscle have been recognized as endocrine organs since they produce and secrete "hormone-like factors" that can mutually influence each other and other tissues, giving rise to a "bone-muscle crosstalk". In our study, we made use of myogenic (C2C12 cells) and osteogenic (2T3 cells) cell lines to investigate the effects of muscle cell-produced factors on the maturation process of osteoblasts. We found that the myogenic medium has inhibitory effects on bone cell differentiation and we identified sclerostin as one of the myokines produced by muscle cells. Sclerostin is a secreted glycoprotein reportedly expressed by bone/cartilage cells and is considered a negative regulator of bone growth due to its role as an antagonist of the Wnt/β-catenin pathway. Given the inhibitory role of sclerostin in bone, we analyzed its expression by muscle cells and how it affects bone formation and homeostasis. Firstly, we characterized and quantified sclerostin synthesis by a myoblast cell line (C2C12) and by murine primary muscle cells by Western blotting, real-time PCR, immunofluorescence, and ELISA assay. Next, we investigated in vivo production of sclerostin in distinct muscle groups with different metabolic and mechanical loading characteristics. This analysis was done in mice of different ages (6 weeks, 5 and 18 months after birth) and revealed that sclerostin expression is dynamically modulated in a muscle-specific way during the lifespan. Finally, we transiently expressed sclerostin in the hind limb muscles of young mice (2 weeks of age) via in vivo electro-transfer of a plasmid containing the gene in order to investigate the effects of muscle-specific overproduction of the protein. Our data disclosed an inhibitory role of the muscular sclerostin on the bones adjacent to the electroporated muscles. This observation suggests that sclerostin released by skeletal muscle might synergistically interact with osseous sclerostin and potentiate negative regulation of osteogenesis possibly by acting in a paracrine/local fashion. Our data point out a role for muscle as a new source of sclerostin.
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http://dx.doi.org/10.3390/biomedicines9010071DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7828203PMC
January 2021

Volumetric Changes Following Lateral Guided Bone Regeneration.

Int J Oral Maxillofac Implants 2020 Sep/Oct;35(5):e77-e85

Resorbable membranes are well described and employed for horizontal guided bone regeneration (GBR). However, the currently available literature does not provide information on the bone volumetric changes during the healing that follows GBR procedures and dental implant placement. Therefore, the aim of this pilot study was to initially analyze the volumetric bone changes after treating pristine edentulous mandibular defects with lateral GBR using freeze-dried bone allograft (FDBA) and collagen resorbable membrane. Six patients were selected for the analysis. Clinical changes in bone volume before and after GBR were measured. In addition, digital volumetric analysis of the augmented ridges was performed preoperatively, as well as 4 and 6 months after the GBR procedure. At the time of dental implant placement, bone cores were collected during the osteotomy for histologic analysis. Data on volume changes showed a mean of 297.5 ± 134 mm augmented bone volume at 4 months with 5% ± 3.78% resorption from 4 to ≥ 6 months. Histologic bone core analysis showed 44.9% plusmn; 5.1% mineralization in the area of augmentation. Within the limitations of this pilot study, resorbable membranes exhibited reliability for GBR in intercalated mandibular defects, providing sufficient bone volume gain at ≥ 6 months for implant stabilization and limited resorption during graft healing.
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http://dx.doi.org/10.11607/jomi.7524DOI Listing
October 2020

WISP-2 expression induced by Teriparatide treatment affects in vitro osteoblast differentiation and improves in vivo osteogenesis.

Mol Cell Endocrinol 2020 08 18;513:110817. Epub 2020 May 18.

Department of Biomedical, Metabolic and Neural Sciences, Section of Human Morphology, University of Modena and Reggio Emilia, Modena, Italy.

The Osteocyte, recognized as a major orchestrator of osteoblast and osteoclast activity, is the most important key player during bone remodeling processes. Imbalances occurring during bone remodeling, caused by hormone perturbations or by mechanical loading alterations, can induce bone pathologies such as osteoporosis. Recently, the active fraction of parathormone, PTH (1-34) or Teriparatide (TPTD), was chosen as election treatment for osteoporosis. The effect of such therapy is dependent on the temporal manner of administration. The molecular reasons why the type of administration regimen is so critical for the fate of bone remodeling are numerous and not yet well known. Our study attempts to analyze diverse signaling pathways directly activated in osteocytes upon TPTD treatment. By means of gene array analysis, we found many molecules upregulated or downregulated in osteocytes. Later, we paid attention to Wisp-2, a protein involved in the Wnt pathway, that is secreted by MLO-Y4 cells and increases upon TPTD treatment and that is able to positively influence the early phases of osteogenic differentiation. We also confirmed the pro osteogenic property of Wisp-2 during mesenchymal stem cell differentiation into the preliminary osteoblast phenotype. The same results were confirmed with an in vivo approach confirming a remarkable Wisp-2 expression in metaphyseal trabecular bone. These results highlighted the anabolic roles unrolled by osteocytes in controlling the action of neighboring cells, suggesting that the perturbation of certain signaling cascades, such as the Wnt pathway, is crucial for the positive regulation of bone formation.
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http://dx.doi.org/10.1016/j.mce.2020.110817DOI Listing
August 2020

Scleral ossicles: angiogenic scaffolds, a novel biomaterial for regenerative medicine applications.

Biomater Sci 2019 Dec;8(1):413-425

Department of Biomedical, Metabolic Science and Neuroscience, University of Modena and Reggio Emilia, 41125 Modena, Italy.

Given the current prolonged life expectancy, various pathologies affect increasingly the aging subjects. Regarding the musculoskeletal apparatus, bone fragility induces more susceptibility to fractures, often not accompanied by good ability of self-repairing, in particular when critical-size defects (CSD) occur. Currently orthopedic surgery makes use of allografting and autografting which, however, have limitations due to the scarce amount of tissue that can be taken from the donor, the possibility of disease transmission and donor site morbidity. The need to develop new solutions has pushed the field of tissue engineering (TE) research to study new scaffolds to be functionalized in order to obtain constructs capable of promoting tissue regeneration and achieve stable bone recovery over time. This investigation focuses on the most important aspect related to bone tissue regeneration: the angiogenic properties of the scaffold to be used. As an innovative solution, scleral ossicles (SOs), previously characterized as natural, biocompatible and spontaneously decellularized scaffolds used for bone repair, were tested for angiogenic potential and biocompatibility. To reach this purpose, in ovo Chorioallantoic Membrane Assay (CAM) was firstly used to test the angiogenic potential; secondly, in vivo subcutaneous implantation of SOs (in a rat model) was performed in order to assess the biocompatibility and the inflammatory response. Finally, thanks to the analysis of mass spectrometry (LCMSQE), the putative proteins responsible for the SO angiogenic properties were identified. Thus, a novel natural biomaterial is proposed, which is (i) able to induce an angiogenic response in vivo by subcutaneous implantation in a non-immunodeficient animal model, (ii) which does not induce any inflammatory response, and (iii) is useful for regenerative medicine application for the healing of bone CSD.
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http://dx.doi.org/10.1039/c9bm01234fDOI Listing
December 2019

Interaction among Calcium Diet Content, PTH (1-34) Treatment and Balance of Bone Homeostasis in Rat Model: The Trabecular Bone as Keystone.

Int J Mol Sci 2019 Feb 11;20(3). Epub 2019 Feb 11.

Department of Biomedical, Metabolic and Neural Sciences, Section of Human Morphology, University of Modena and Reggio Emilia, 41124 Modena, Italy.

The present study is the second step (concerning normal diet restoration) of the our previous study (concerning the calcium-free diet) to determine whether normal diet restoration, with/without concomitant PTH (1-34) administration, can influence amounts and deposition sites of the total bone mass. Histomorphometric evaluations and immunohistochemical analysis for Sclerostin expression were conducted on the vertebral bodies and femurs in the rat model. The final goals are (i) to define timing and manners of bone mass changes when calcium is restored to the diet, (ii) to analyze the different involvement of the two bony architectures having different metabolism (i.e., trabecular versus cortical bone), and (iii) to verify the eventual role of PTH (1-34) administration. Results evidenced the greater involvement of the trabecular bone with respect to the cortical bone, in response to different levels of calcium content in the diet, and the effect of PTH, mostly in the recovery of trabecular bony architecture. The main findings emerged from the present study are (i) the importance of the interplay between mineral homeostasis and skeletal homeostasis in modulating and guiding bone's response to dietary/metabolic alterations and (ii) the evidence that the more involved bony architecture is the trabecular bone, the most susceptible to the dynamical balance of the two homeostases.
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http://dx.doi.org/10.3390/ijms20030753DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6387065PMC
February 2019

Sodium hypochlorite penetration into dentinal tubules after manual dynamic agitation and ultrasonic activation: a histochemical evaluation.

Odontology 2018 Oct 28;106(4):454-459. Epub 2018 Mar 28.

Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, Modena, Italy.

The aim of this study was to compare the effects of Manual Dynamic Agitation and Passive Ultrasonic Irrigation on sodium hypochlorite (NaOCl) penetration into dentinal tubules using its bleaching ability. Thirty-four single-rooted teeth with round-shaped root canals were distributed in two homogeneous groups and one control group, characterized by different NaOCl activation systems: Manual Dynamic Agitation and Passive Ultrasonic Irrigation. After instrumentation, all root canals were stained with 10% copper sulphate solution followed by 1% rubeanic acid alcohol solution under vacuum. Final irrigation was performed with 5 mL of 5.25% NaOCl solution for 1 min and activated with Manual Dynamic Agitation or Passive Ultrasonic Irrigation for another 1 min depending on the treatment group. The teeth were transversely sectioned at the middle portion of the apical, middle, and coronal thirds and observed under light microscope. NaOCl solution penetration was evaluated by measuring the percentage of bleached circumference of the root canal relative to the stained circumference, bleached areas, mean, and maximum penetration depth. No differences in the evaluated parameters were observed between groups (p > 0.05). Within groups, an increase of values was recorded from apical to coronal direction as for percentage of staining, percentage of bleaching and bleached area. NaOCl penetration into dentinal tubules did not significantly vary among the three levels. No significant differences in penetration of sodium hypochlorite into dentinal tubules when activated by means of Manual Dynamic Agitation or Passive Ultrasonic Irrigation were observed in the apical, middle, and coronal thirds of teeth with single straight round root canals.
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http://dx.doi.org/10.1007/s10266-018-0355-4DOI Listing
October 2018

Structural and ultrastructural analyses of bone regeneration in rabbit cranial osteotomy: Piezosurgery versus traditional osteotomes.

J Craniomaxillofac Surg 2018 Jan 12;46(1):107-118. Epub 2017 Oct 12.

Dipartimento di Scienze Biomediche, Metaboliche e Neuroscienze, Sezione di Morfologia Umana, Università di Modena e Reggio Emilia, via del Pozzo 71, 41124, Modena, Italy.

Clinical advantages of piezosurgery have been already proved. However, few investigations have focused on the dynamics of bone healing. The aim of this study was to evaluate, in adult rabbits, bone regeneration after cranial linear osteotomies with two piezoelectrical devices (Piezosurgery Medical - PM and Piezosurgery Plus - PP), comparing them with conventional rotary osteotomes (RO). PP was characterized by an output power three times higher than PM. Fifteen days after surgery, histomorphometric analyses showed that the osteotomy gap produced with PM and PP was about half the size of that produced by RO, and in a more advanced stage of recovery. Values of regenerated bone area with respect to the total osteotomy area were about double in PM and PP samples compared with RO ones, while the number of TRAP-positive (tartrate-resistant acid phosphatase positive) osteoclasts per linear surface showed a significant increase, suggesting greater bone remodelling. Under scanning electron microscopy, regenerated bone displayed higher cell density and less mineralized matrix compared with pre-existent bone for all devices used. Nanoindentation tests showed no changes in elastic modulus. In conclusion, PM/PP osteotomies can be considered equivalent to each other, and result in more rapid healing compared with those using RO.
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http://dx.doi.org/10.1016/j.jcms.2017.10.004DOI Listing
January 2018

Expression and functional proteomic analyses of osteocytes from Xenopus laevis tested under mechanical stress conditions: preliminary observations on an appropriate new animal model.

J Anat 2017 Dec 19;231(6):823-834. Epub 2017 Sep 19.

Dipartimento di Scienze Biomediche Metaboliche e Neuroscienze, Sezione di Morfologia umana. Università degli Studi di Modena e Reggio Emilia, Modena, Italy.

Hitherto, the role of the osteocyte as transducer of mechanical stimuli into biological signals is far from settled. In this study, we used an appropriate model represented by the cortex of Xenopus laevis long bone diaphysis lacking (unlike the mammalian one) of vascular structures and containing only osteocytes inside the bone matrix. These structural features allow any change of protein profile that might be observed upon different experimental conditions, such as bone adaptation to stress/mechanical loading, to be ascribed specifically to osteocytes. The study was conducted by combining ultrastructural observations and two-dimensional electrophoresis for proteomic analysis. The osteocyte population was extracted from long bones of lower limbs of amphibian skeletons after different protocols (free and forced swimming). The experiments were performed on 210 frogs subdivided into five trials, each including free swimming frogs (controls) and frogs submitted to forced swimming (stressed). The stressed groups were obliged to swim (on movable spheres covering the bottom of a pool on a vibrating plate) continuously for 8 h, and killed 24 h later along with the control groups. Long bones free of soft tissues (periosteum, endosteum and bone marrow), as well as muscles of posterior limbs, were processed and analyzed for proteins differentially expressed or phosphorylated between the two sample groups. The comparative analysis showed that protein phosphorylation profiles differ between control and stressed groups. In particular, we found in long bones of stressed samples that both Erk1/2 and Akt are hyperphosphorylated; moreover, the different phosphorylation of putative Akt substrates (recognized by specific Akt phosphosubstrates-antibody) in stressed vs. control samples clearly demonstrated that Akt signaling is boosted by forced swimming (leading to an increase of mechanical stress) of amphibian long bones. In parallel, we found in posterior limb muscles that the expression of heat shock protein HSP27 and HSP70 stress markers increased upon the forced swimming condition. Because the cortexes of frog long bones are characterized by the presence of only osteocytes, all our results establish the suitability of the X. laevis animal model to study the bone response to stress conditions mediated by this cell type and pave the way for further analysis of the signaling pathways involved in these signal transduction mechanisms.
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http://dx.doi.org/10.1111/joa.12685DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5696140PMC
December 2017

Plaque accumulation on titanium disks with different surface treatments: an in vivo investigation.

Odontology 2018 Apr 22;106(2):145-153. Epub 2017 Aug 22.

Department of Surgery, Medicine, Dentistry and Morphological Sciences with Transplant Surgery, Oncology and Regenerative Medicine Relevance, School of Dentistry, University of Modena and Reggio Emilia, Modena, Italy.

Implants with rough surfaces are today widely used. It has been speculated that rough surfaces (Ra > 0.2 μm) provide a better "substrate" for retention and accumulation of plaque in terms of area, thickness and colony-forming unit that can eventually lead to peri mucositis and/or peri-implantitis. The aim of this investigation was to evaluate in vivo the plaque accumulation after 48 h on three implant surfaces with different treatments. For this investigation, we used 21 sterilized titanium disks, with a diameter of 8mm and a thickness of 3 mm, provided by the manufacturer: 7 with machined surface, as smooth control, 7 with HA grit sandblasted RBM surface and 7 with Ca incorporated in titanium Xpeed surface. One disk for each surface treatment was characterized at time 0 by SEM and AFM to study, respectively, the surface morphology and roughness. The other 18 disks were mounted randomly on three upper acrylic bites in a buccal lateral position, worn for 48 h by three volunteer students for plaque accumulation. After 48 h each disk was removed and analyzed qualitatively and quantitatively by an independent operator, not involved into the study, in order to avoid bias. Data collected were statistically analyzed by one-way ANOVA. The qualitative analysis showed no differences in terms of total plaque accumulation between the surfaces. Data from quantitative analysis using Anova Test showed no significance between all groups. In this in vivo investigation all the surfaces studied promoted plaque formation. The degree of surface roughness seems not to be a critical factor for plaque accumulation.
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http://dx.doi.org/10.1007/s10266-017-0317-2DOI Listing
April 2018

Biocompatibility Analyses of Al₂O₃-Treated Titanium Plates Tested with Osteocyte and Fibroblast Cell Lines.

Biomedicines 2017 Jun 16;5(2). Epub 2017 Jun 16.

Dipartimento di Scienze Biomediche, Metaboliche e Neuroscienze, Sezione di Morfologia Umana, Università di Modena e R.E, 41124 Modena, Italy.

Osseointegration of a titanium implant is still an issue in dental/orthopedic implants durable over time. The good integration of these implants is mainly due to their surface and topography. We obtained an innovative titanium surface by shooting different-in-size particles of Al₂O₃ against the titanium scaffolds which seems to be ideal for bone integration. To corroborate that, we used two different cell lines: MLO-Y4 (murine osteocytes) and 293 (human fibroblasts) and tested the titanium scaffolds untreated and treated (i.e., Al₂O₃ shot-peened titanium surfaces). Distribution, density, and expression of adhesion molecules (fibronectin and vitronectin) were evaluated under scanning electron microscope (SEM) and confocal microscope (CM). DAPI and fluorochrome-conjugated antibodies were used to highlight nuclei, fibronectin, and vitronectin, under CM; cell distribution was analyzed after gold-palladium sputtering of samples by SEM. The engineered biomaterial surfaces showed under SEM irregular morphology displaying variously-shaped spicules. Both SEM and CM observations showed better outcome in terms of cell adhesion and distribution in treated titanium surfaces with respect to the untreated ones. The results obtained clearly showed that this kind of surface-treated titanium, used to manufacture devices for dental implantology: (i) is very suitable for cell colonization, essential prerequisite for the best osseointegration, and (ii) represents an excellent solution for the development of further engineered implants with the target to obtain recovery of stable dental function over time.
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http://dx.doi.org/10.3390/biomedicines5020032DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5489818PMC
June 2017

Effect of Different Irrigation Systems on Sealer Penetration into Dentinal Tubules.

J Endod 2017 Apr;43(4):652-656

Department of Surgery, Medicine, Dentistry and Morphological Sciences with Transplant Surgery, Oncology and Regenerative Medicine Relevance (CHIMOMO), University of Modena and Reggio Emilia, Modena, Italy.

Introduction: Different irrigation systems have been developed to improve the efficacy and distribution of the irrigants. The aim of this study was to compare the effect of conventional endodontic needle irrigation with other irrigant delivery and/or agitation systems on sealer penetration into dentinal tubules.

Methods: Fifty single-rooted teeth with round-shaped root canals were distributed in 5 homogeneous groups characterized by the different cleansing system used: conventional endodontic needle irrigation, EndoActivator, Irrisafe, Self-Adjusting File, and EndoVac. After instrumentation, all teeth were filled by Thermafil obturators and rhodamine B dye labeled TopSeal sealer. Teeth were transversally sectioned at 2-, 5-, and 7-mm levels from the apex and observed under confocal laser scanning microscope. Maximum, mean, and percentage of sealer penetration inside tubules around the root canal were measured. Moreover, the integrity of the sealer layer perimeter was evaluated.

Results: No significant differences both in mean (p > .05) and in maximum penetration depth (p > .05) were observed among groups, whereas both parameters showed an increased trend within each group from the 2- to the 7-mm level from apex. Similarly, the percentage of penetration around the root canal wall did not differ among groups (p > .05) and showed an increasing trend within each group from the apical to the coronal portion of the canal.

Conclusions: Sealer penetration into dentinal tubules is not affected by the irrigant delivery and/or agitation systems studied. Thermafil with TopSeal technique achieves complete sealer perimeter integrity in all groups.
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http://dx.doi.org/10.1016/j.joen.2016.12.004DOI Listing
April 2017

PTH(1-34) effects on repairing experimentally drilled holes in rat femur: novel aspects - qualitative vs. quantitative improvement of osteogenesis.

J Anat 2017 01 15;230(1):75-84. Epub 2016 Aug 15.

Dipartimento di Scienze Biomediche, Metaboliche e Neuroscienze - Sez. Morfologia umana, Università di Modena e Reggio Emilia, Modena, Italy.

The timetable of effects on bone repair of the active fraction-parathyroid hormone, PTH(1-34), was analytically investigated from the morphometric viewpoint in 3-month-old male Sprague-Dawley rats, whose femurs were drilled at mid-diaphyseal level (transcortical holes). The animals were divided into groups with/without PTH(1-34) administration, and sacrificed at different times (10, 28, 45 days after surgery). The observations reported here need to be framed in the context of our previous investigations regarding bone histogenesis (Ferretti et al. Anat Embryol. 2002; 206: 21-29) in which we demonstrated the occurrence of two successive bone-forming processes during both skeletal organogenesis and bone repair, i.e. static and dynamic osteogenesis: the former (due to stationary osteoblasts, haphazardly grouped in cords) producing preliminary bad quality trabecular bone, the latter (due to typical polarized osteoblasts organized in ordered movable laminae) producing mechanically valid bone tissue. The primary function of static osteogenesis is to provide a rigid scaffold containing osteocytes (i.e. mechano-sensors) for osteoblast laminae acting in dynamic osteogenesis. In the present work, histomorphometric analysis revealed that, already 10 days after drilling, despite the holes being temporarily filled by the same amount of newly formed trabecular bone by static osteogenesis independently of the treatment, the extent of the surface of movable osteoblast-laminae (covering the trabecular surface) was statistically higher in animals submitted to PTH(1-34) administration than in control ones; this datum strongly suggests the effect of PTH(1-34) alone in anticipating the occurrence of dynamic osteogenesis involved in the production of good quality bone (with more ordered collagen texture) more suitable for loading. This study could be crucial in further translational clinical research in humans for defining the best therapeutic strategies to be applied in recovering severe skeletal lesions, particularly as regards the time of PTH(1-34) administration.
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http://dx.doi.org/10.1111/joa.12533DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5192790PMC
January 2017

Feasibility of Electroporation in Bone and in the Surrounding Clinically Relevant Structures: A Preclinical Investigation.

Technol Cancer Res Treat 2016 12 7;15(6):737-748. Epub 2015 Sep 7.

Laboratory of Preclinical and Surgical Studies, Rizzoli Orthopaedic Institute, Bologna, Italy.

Skeletal metastases are a common cause of severe morbidity, reduction in quality of life and often early mortality. Consequently, improvements in therapies are necessary. Electroporation uses electric energy to alter cancer cell membrane permeability and enhance the local uptake of chemotherapeutics, thus leading to local tumor control. The aim of this study was to investigate the feasibility and safety of delivering electric field protocols causing electroporation of healthy bone and structures of clinical relevance using small and large animal models. Reversible electroporation was used in the rabbit sciatic nerve by applying 2 series of 8 pulses 100ms long at 1000 V/cm. Irreversible electroporation was used in rabbit distal femur condyles and in sheep vertebral body by applying 120 pulses 100ms long at 1750 V/cm. Any effect on surrounding sensitive structures was investigated. Reversible electroporation of sciatic nerve was associated with transient foot functional deficit that completely recovered at 30 days. Irreversible electroporation removed cells from trabeculae in the femurs of rabbits and in the vertebral body of sheep. After irreversible protocol, histology and microtomography demonstrated that the trabecular structure was maintained, the presence of new bone marrow cells, osteoblasts, and mineral apposition characterized by new trabeculae thinner than controls (P = .005) and a significant reduction in the ablated areas (-225%, P = .0219). Spinal cord, vertebral pedicles and spinal nerves showed transient edema in the absence of functional or structural alterations. Collectively, these results show that electroporation can be safely applied to bone even in the proximity of neuronal structures.
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http://dx.doi.org/10.1177/1533034615604454DOI Listing
December 2016

Mineral and Skeletal Homeostasis Influence the Manner of Bone Loss in Metabolic Osteoporosis due to Calcium-Deprived Diet in Different Sites of Rat Vertebra and Femur.

Biomed Res Int 2015 4;2015:304178. Epub 2015 May 4.

Dipartimento di Scienze Biomediche, Metaboliche e Neuroscienze-Sezione di Morfologia Umana, Università di Modena e Reggio Emilia, Istituti Anatomici, 41124 Modena, Italy.

Rats fed calcium-deprived diet develop osteoporosis due to enhanced bone resorption, secondary to parathyroid overactivity resulting from nutritional hypocalcemia. Therefore, rats provide a good experimental animal model for studying bone modelling alterations during biochemical osteoporosis. Three-month-old Sprague-Dawley male rats were divided into 4 groups: (1) baseline, (2) normal diet for 4 weeks, (3) calcium-deprived diet for 4 weeks, and (4) calcium-deprived diet for 4 weeks and concomitant administration of PTH (1-34) 40 µg/Kg/day. Histomorphometrical analyses were made on cortical and trabecular bone of lumbar vertebral body as well as of mid-diaphysis and distal metaphysis of femur. In all rats fed calcium-deprived diet, despite the reduction of trabecular number (due to the maintenance of mineral homeostasis), an intense activity of bone deposition occurs on the surface of the few remaining trabeculae (in answering to mechanical stresses and, consequently, to maintain the skeletal homeostasis). Different responses were detected in different sites of cortical bone, depending on their main function in answering mineral or skeletal homeostasis. This study represents the starting point for work-in-progress researches, with the aim of defining in detail timing and manners of evolution and recovery of biochemical osteoporosis.
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http://dx.doi.org/10.1155/2015/304178DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4434225PMC
March 2016

Effect of electric current stimulation in combination with external fixator on bone healing in a sheep fracture model.

Vet Ital 2014 Dec;50(4):249-57

Clinica Chirurgica Veterinaria, Università degli Studi di Teramo, Piazza A. Moro 45, 64100 Teramo, Italy.

Biophysical stimulations with electric and electromagnetic fields have been demonstrated to accelerate the bone-healing rate. This study has been designed to investigate the effects of electricity directly connected with the central pins of an external fixator in an experimental osteotomy model in sheep. Thirty mg/kg of tetracycline chloride were administered on the 30th and on the 45th day after surgery for histomorphometric studies. Plain radiographs were obtained in standard projections every 15 days after surgery and were analyzed with a software program (Corel Photo-Paint Pro X2, Corel Corporation, Ottawa, Canada). The specimens obtained after 60 days were examined with histological analysis. The results show that biophysical treatment with alternating electricity in combination with external fixator enhances new-bone formation. The translational value of this study, due to the similarities between ovine and human species, suggests that this treatment could be useful in speeding the bone-healing rate both in animals and humans.
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http://dx.doi.org/10.12834/VetIt.271.963.2DOI Listing
December 2014

Ferutinin dose-dependent effects on uterus and mammary gland in ovariectomized rats.

Histol Histopathol 2014 Aug 10;29(8):1027-37. Epub 2014 Feb 10.

Dipartimento di Scienze Biomediche, Metaboliche e Neuroscienze, Sezione di Morfologia umana, Università di Modena e Reggio Emilia, Modena, Italy.

The present paper completes our recent study on the effects of phytoestrogen ferutinin in preventing osteoporosis and demonstrating the superior osteoprotective effect of a 2 mg/kg/day dose in ovariectomized (OVX) rats, compared to both estrogens and lower (0.5, 1 mg/kg/day) ferutinin doses. Morphological and morphometrical analyses were performed on the effects of different doses of ferutinin administrated for one month on uterus and on mammary gland of Sprague-Dawley OVX rats, evaluated in comparison with the results for estradiol benzoate. To verify whether ferutinin provides protection against uterine and breast cancer, estimations were made of both the amount of cell proliferation (by Ki-67), and the occurrence of apoptosis (by TUNEL), two processes that in unbalanced ratio form the basis for cancer onset. The results suggest that the effects of ferutinin are dose dependent and that a 2 mg/kg/day dose might offer a better protective action against the onset of both breast and uterine carcinoma compared to ferutinin in lower doses or estradiol benzoate, increasing cellular apoptosis in glandular epithelia.
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http://dx.doi.org/10.14670/HH-29.1027DOI Listing
August 2014

Morphological and quantitative analysis of BCL6 expression in human colorectal carcinogenesis.

Oncol Rep 2014 Jan 13;31(1):103-10. Epub 2013 Nov 13.

Department of Biomedical, Metabolic and Neurosciences, Section of Human Morphology, University of Modena and Reggio Emilia, Modena, Italy.

The aim of the present study was to determine whether BCL6 is expressed during malignant transformation of the large bowel and to assess whether, and to what extent, immunoreactivity is related to the different stages of neoplastic progression. Samples of normal colorectal mucosa (n=22), microadenomas (n=22) and colorectal cancer (n=22), were analyzed by immunohistochemistry, immunofluorescence coupled with confocal microscopy and western blotting. Our results clearly outlined the marked increase occurring in both intensity and density of BCL6 protein expression in the normal mucosa-microadenoma-carcinoma sequence. Immunohistochemistry and immunofluorescence analyses showed that BCL6 is expressed at low levels in normal mucosa and increases in microadenoma and in cancer with statistical significance. These results were confirmed by western blotting data. The increasing expression of BCL6 in human colorectal cancer development suggests the involvement of BCL6 in tumor progression, from the earliest stages of carcinogenesis with significant increase in cancer. The enhanced understanding of the biological role of BCL6, previously shown to exert a key role in lymphomagenesis, may lead to a re-evaluation of this protein and may highlight the importance of performing further studies in order to identify novel therapeutic targets for colorectal cancer.
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http://dx.doi.org/10.3892/or.2013.2846DOI Listing
January 2014

Differential efficacy of endodontic obturation procedures: an ex vivo study.

Odontology 2014 Jul 9;102(2):223-31. Epub 2013 Jul 9.

Dipartimento di Medicina Diagnostica, Clinica e di Sanità Pubblica, Università di Modena e Reggio Emilia, Istituti Biologici (2° piano), Via Campi, 287, 41125, Modena, Italy.

By means of a double-chamber model, different root canal filling materials and procedures were compared. Briefly, the root canals of single-rooted human teeth, extracted for periodontal reasons, were instrumented and obturated by gutta-percha/Pulp Canal Sealer EWT (PCS) or by Resilon, in association with different sealers (Real Seal, RelyX Unicem or Meta). Obturation was achieved by traditional continuous wave of condensation technique (TCWCT), a modified version of it (MCWCT), or single cone technique (SCT). The obturated roots, inserted in a double-chamber model, were sterilized by gamma irradiation. Next, Enterococcus faecalis was added to the upper chamber and the specimens were incubated at 37 °C for up to 120 days; the development of turbidity in the lower chambers' broths indicated bacterial leakage through the obturated root canals. The kinetics of leakage were analyzed in different groups by means of Kaplan-Meier statistics and compared by log-rank test. The results showed that root canals obturated with either gutta-percha/PCS using the MCWCT, Resilon/Real Seal SCT or Resilon/RelyX Unicem using the TCWCT displayed significantly better performance than the remaining groups (p < 0.01). Histological evaluation, performed to investigate microbial localization inside specimens, confirmed that this parameter varied according to the obturation procedures and materials employed. This ex vivo study indicates that gutta-percha/PCS, if used with the MCWCT, is as effective as Resilon when coupled to Real Seal with the SCT or, interestingly, to RelyX Unicem with the TCWCT. These data suggest that further improvement of the currently employed root canal filling procedures is achievable, depending on both the filling materials and the technique employed, thus encouraging clinical studies in this direction.
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http://dx.doi.org/10.1007/s10266-013-0125-2DOI Listing
July 2014

Effects of different doses of ferutinin on bone formation/resorption in ovariectomized rats.

J Bone Miner Metab 2012 Nov 25;30(6):619-29. Epub 2012 Jul 25.

Dipartimento di Scienze biomediche, Sezione di Morfologia umana, Istituti Anatomici, Università di Modena e Reggio Emilia, Modena, Italy.

This study analyzes the effects of different doses of ferutinin on bone loss caused by estrogen deficiency in ovariectomized rats, in comparison with estradiol benzoate. Thirty female Sprague-Dawley rats were ovariectomized and treated for 30 days from the day after ovariectomy. Static/dynamic histomorphometric analyses were performed on trabecular and cortical bone of lumbar vertebrae and femurs. Very low weight increments were recorded only in all F-OVX groups, with respect to the others. Although the great differences in weight, that could imply a decrease of bone mass in F-OVX groups compared to the control ovariectomized group (C-OVX), trabecular bone in lumbar vertebrae did not show significant differences, suggesting that ferutinin, opposing estrogen deficiency, inhibits bone resorption. Newly formed cortical bone was always low in all F-OVX groups and high in C-OVX, suggesting that it is mainly devoted in answering mechanical demands. In contrast, in distal femoral metaphyses, trabecular bone was reduced and the number of osteoclasts was increased in C-OVX with respect to all other groups, suggesting that it is mainly devoted in answering metabolic demands; moreover, ferutinin dose of 2 mg/kg seemed to be more effective than the lower doses used and estrogens, particularly in those skeletal regions with higher metabolic activity. Our results suggest that the role of ferutinin in preventing osteoporosis caused by estrogen deficiency is expressed in decreasing bone erosion; moreover, in all F-OVX groups bone turnover is very low and seems correlated to the trivial body weight increase, which, in turn, depends on ferutinin treatment.
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http://dx.doi.org/10.1007/s00774-012-0366-0DOI Listing
November 2012

Immunocytochemical and structural comparative study of committed versus multipotent stem cells cultured with different biomaterials.

Micron 2013 Apr 6;47:1-9. Epub 2012 Mar 6.

Department of Biomedical Sciences, Section of Human Morphology, University of Modena and Reggio Emilia, Italy.

The aim of this work was the comparison of the behavior of committed (human osteoblast cells - hOB - from bone biopsies) versus multipotent (human dental pulp stem cells - hDPSC - from extracted teeth) cells, cultured on shot-peened titanium surfaces, since the kind of cell model considered has been shown to be relevant in techniques widely used in studies on composition/morphology of biomaterial surfaces. The titanium surface morphology, with different roughness, and the behavior of cells were analyzed by confocal microscope (CM), scanning electron microscope (SEM) and X-ray microanalysis. The best results, in terms of hOB adhesion/distribution, were highlighted by both CM and SEM in cultured plates having 20-μm-depth cavities. On the contrary, CM and SEM results highlighted the hDPSC growth regardless the different surface morphology, arranged in overlapped layers due to their high proliferation rate, showing their unfitness in biomaterial surface test. Nevertheless, hDPSC cultured inside 3D-matrices reproduced an osteocyte-like three-dimensional network, potentially useful in the repair of critical size bone defects. The behavior of the two cell models suggests a different use in biomaterial cell cultures: committed osteoblast cells could be appropriate in selecting the best surfaces to improve osseointegration, while multipotent cells could be suitable to obtain in vitro osteocyte-like network for regenerative medicine. The originality of the present work consists in studying for the first time two different cell models (committed versus multipotent) compared in parallel different biomaterial cultures, thus suggesting distinct targets for each cellular model.
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http://dx.doi.org/10.1016/j.micron.2012.02.017DOI Listing
April 2013

Osteocyte apoptosis and absence of bone remodeling in human auditory ossicles and scleral ossicles of lower vertebrates: a mere coincidence or linked processes?

Calcif Tissue Int 2012 Mar 31;90(3):211-8. Epub 2012 Jan 31.

Dipartimento di Scienze Biomediche, Sezione di Morfologia umana-Istituti Anatomici, Università di Modena e Reggio Emilia, Via del Pozzo 71 (area Policlinico), 41125 Modena, Italy.

Considering the pivotal role as bone mechanosensors ascribed to osteocytes in bone adaptation to mechanical strains, the present study analyzed whether a correlation exists between osteocyte apoptosis and bone remodeling in peculiar bones, such as human auditory ossicles and scleral ossicles of lower vertebrates, which have been shown to undergo substantial osteocyte death and trivial or no bone turnover after cessation of growth. The investigation was performed with a morphological approach under LM (by means of an in situ end-labeling technique) and TEM. The results show that a large amount of osteocyte apoptosis takes place in both auditory and scleral ossicles after they reach their final size. Additionally, no morphological signs of bone remodeling were observed. These facts suggest that (1) bone remodeling is not necessarily triggered by osteocyte death, at least in these ossicles, and (2) bone remodeling does not need to mechanically adapt auditory and scleral ossicles since they appear to be continuously submitted to stereotyped stresses and strains; on the contrary, during the resorption phase, bone remodeling might severely impair the mechanical resistance of extremely small bony segments. Thus, osteocyte apoptosis could represent a programmed process devoted to make stable, when needed, bone structure and mechanical resistance.
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http://dx.doi.org/10.1007/s00223-012-9569-6DOI Listing
March 2012

Structural and histomorphometric evaluations of ferutinin effects on the uterus of ovariectomized rats during osteoporosis treatment.

Life Sci 2012 Jan 9;90(3-4):161-8. Epub 2011 Nov 9.

Section of Human Morphology of the Department of Biomedical Sciences, University of Modena and Reggio Emilia, Modena, Italy.

Aims: The effects of chronic administration of Ferutinin (phytoestrogen found in the plants of genus Ferula), compared with those elicited by estradiol benzoate, were evaluated, following ovariectomy, on the uterus of ovariectomized rats as regard weight, size, structure and histomorphometry.

Main Methods: The experimental study included 40 female Sprague-Dawley rats, assigned to two different protocols, i.e. preventive and recovering. In the preventive protocol, ferutinin (2mg/kg/day) was orally administered for 30days, starting from the day after ovariectomy; in the recovering protocol, ferutinin was administered, at the same dosage, for 30days starting from the 60th day after ovariectomy, when osteoporosis was clearly established. Its effects were compared with those of estradiol benzoate (1.5μg per rat twice a week, subcutaneously injected) vs. vehicle-treated ovariectomized controls and vehicle-treated sham-operated controls. Uteri were removed, weighed and analysed under both the structural and histomorphometrical points of view.

Key Findings: Our data show that ferutinin acts, similarly to estradiol benzoate, on the uterus stimulating endometrial and myometrial hypertrophy; this notwithstanding, the phytoestrogen ferutinin, in contrast to estrogen treatment, appears to increase apoptosis in uterine luminal and glandular epithelia.

Significance: Ferutinin, used in osteoporosis treatment primarily for bone mass recovering, seems in line with an eventual protective function against uterine carcinoma, unlike estrogens so far employed in hormone replacement therapy (HRT).
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http://dx.doi.org/10.1016/j.lfs.2011.11.001DOI Listing
January 2012

Influence of ferutinin on bone metabolism in ovariectomized rats. II: role in recovering osteoporosis.

J Anat 2010 Jul 10;217(1):48-56. Epub 2010 May 10.

Department of Anatomy and Histology, Section of Human Anatomy, University of Modena and RE, Modena, Italy.

The aim of the present investigation, which represents an extension of a previous study, was to investigate the effect of ferutinin in recovering severe osteoporosis due to estrogen deficiency after rat ovariectomy and to compare phytoestrogen effects with those of estrogens commonly used in hormone replacement therapy (HRT) by women with postmenopausal osteoporosis. The animal model used was the Sprague-Dawley ovariectomized rat. Ferutinin was orally administered (2 mg kg(-1) per day) for 30 or 60 days starting from 2 months after ovariectomy (i.e. when osteoporosis was clearly evident) and its effects were compared with those of estradiol benzoate (1.5 microg per rat twice a week, subcutaneously injected) vs. vehicle-treated ovariectomized (OVX) and sham-operated (SHAM) rats. Histomorphometric analyses were performed on trabecular bone of lumbar vertebrae (4th and 5th) and distal femoral epiphysis, as well as on cortical bone of femoral diaphysis. Bone histomorphometric analyses showed that ferutinin seems to display the same effects on bone mass recorded with estradiol benzoate, thus suggesting that it could enhance the recovery of bone loss due to severe estrogen deficiency in OVX rats. On this basis, the authors propose listing ferutinin among the substances representing a potential alternative for the treatment of postmenopausal osteoporosis, which occurs as a result of estrogen deficiency.
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http://dx.doi.org/10.1111/j.1469-7580.2010.01242.xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2913011PMC
July 2010

Leptin increases growth of primary ossification centers in fetal mice.

J Anat 2009 Nov 6;215(5):577-83. Epub 2009 Aug 6.

Department of Anatomy and Histology - University of Modena and Reggio Emilia, Modena, Italy.

The effect of peripheral leptin on fetal primary ossification centers during the early phases of bone histogenesis was investigated by administration of leptin to pregnant mice. Fourteen pregnant mice were divided into two groups. The treated pregnant group was subcutaneously injected in the intrascapular region with supraphysiologic doses (2 mg kg(-1)) of leptin (Vinci Biochem, Firenze, Italy) in a volume of 0.1 mL per 10 g body weight, at the 7th, 9th and 11th day of gestation. The control group was treated with physiological solution in the same manner and same times as the treated group. The new-born mice were killed 1 day after birth and the primary ossification centers were stained with Alizarin Red S after diaphanizing the soft tissues in 1% potassium hydroxide. The development of both endochondral and intramembranous ossification centers was morphometrically analysed in long bones. The results showed that the ossification centers of mice born by mothers treated with leptin grow more rapidly in both length and cross-sectional area compared with mice born by the untreated mothers. As the development of long bones depends on endochondral ossification occurring at proximal and distal epiphyseal plates as well as on intramembranous ossification along the periosteal surface, it appears that leptin activates the differentiation and proliferation of both chondrocytes and osteoblasts. The role of leptin as a growth factor of cartilage and bone is discussed in the light of the data reported in the literature.
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http://dx.doi.org/10.1111/j.1469-7580.2009.01134.xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2780574PMC
November 2009

ADA-deficient SCID is associated with a specific microenvironment and bone phenotype characterized by RANKL/OPG imbalance and osteoblast insufficiency.

Blood 2009 Oct 24;114(15):3216-26. Epub 2009 Jul 24.

San Raffaele Telethon Institute for Gene Therapy (HSR-TIGET), Milan, Italy.

Adenosine deaminase (ADA) deficiency is a disorder of the purine metabolism leading to combined immunodeficiency and systemic alterations, including skeletal abnormalities. We report that ADA deficiency in mice causes a specific bone phenotype characterized by alterations of structural properties and impaired mechanical competence. These alterations are the combined result of an imbalanced receptor activator of nuclear factor-kappaB ligand (RANKL)/osteoprotegerin axis, causing decreased osteoclastogenesis and an intrinsic defect of osteoblast function with subsequent low bone formation. In vitro, osteoblasts lacking ADA displayed an altered transcriptional profile and growth reduction. Furthermore, the bone marrow microenvironment of ADA-deficient mice showed a reduced capacity to support in vitro and in vivo hematopoiesis. Treatment of ADA-deficient neonatal mice with enzyme replacement therapy, bone marrow transplantation, or gene therapy resulted in full recovery of the altered bone parameters. Remarkably, untreated ADA-severe combined immunodeficiency patients showed a similar imbalance in RANKL/osteoprotegerin levels alongside severe growth retardation. Gene therapy with ADA-transduced hematopoietic stem cells increased serum RANKL levels and children's growth. Our results indicate that the ADA metabolism represents a crucial modulatory factor of bone cell activities and remodeling.
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http://dx.doi.org/10.1182/blood-2009-03-209221DOI Listing
October 2009

Influence of ferutinin on bone metabolism in ovariectomized rats. I: role in preventing osteoporosis.

J Bone Miner Metab 2009 31;27(5):538-45. Epub 2009 Mar 31.

Section of Human Anatomy, Department of Anatomy and Histology, University of Modena and Reggio Emilia, Via del Pozzo 71 (Area policlinico), 41100, Modena, Italy.

Phytoestrogens play a role in maintaining bone mass in the post-menopausal period for their putative function as osteoprotective agents. The aim of the present study was to investigate the influence of Ferutinin, a phytoestrogen found in the plants of Ferula genus, on bone loss in ovariectomized rats. Such an animal model can simulate the various clinical syndromes deriving from osteoporosis. The effect of the daily oral administration of ferutinin to ovariectomized rats (dosed at 2 mg/kg per day for 30 and 60 days) was compared to that of estradiol benzoate (subcutaneously administered at the dose of 1.5 microg/rat twice a week). After the sacrifice, histomorphometrical analyses were performed on trabecular bone of L4-L5 vertebrae and distal femoral metaphysis, as well as on cortical bone of femoral diaphysis; biochemical parameters (bone mineral components and markers) were also evaluated from the rat serum. The histomorphometrical analyses of trabecular and cortical bone from lumbar vertebrae and femur showed that ferutinin has the same antiosteoporotic effect of estradiol benzoate on bone mass, and in some cases is even stronger. This fact suggests that it could prevent osteoporosis caused by severe estrogen deficiency in ovariectomized rats. The possibility of using ferutinin as an alternative to the commonly employed hormonal replacing therapy in post-menopausal women is discussed.
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http://dx.doi.org/10.1007/s00774-009-0070-xDOI Listing
December 2009

Two peculiar conditions following a coma: a clinical case of heterotopic ossification concomitant with keloid formation.

Clin Anat 2008 May;21(4):348-54

Dipartimento di Anatomia e Istologia, Università di Modena e Reggio Emilia, Modena, Italy.

The etiology and formation pattern of heterotopic ossifications (HO) are still unknown. They occur in soft tissues in which bone does not normally form, near one or more proximal joints. In this article, the authors report a peculiar case of a 31-year-old patient affected by scapulo-humeral ankylosis that occurred about 6 months after a coma, in which two unusual concomitant conditions were observed: HO formation in the scapulo-humeral region and the development of keloids during wound repair. The scapulo-humeral ankylosis was resolved surgically with the removal of the HO, which was then studied morphologically to understand its formation pattern. By light microscopy and transmission electron microscopy, it was observed that heterotopic bone displays the normal microscopic structure of primary bone, in which two types of bone tissue were recognized, i.e., woven-fibered bone, deeply located and produced first, and lamellar bone. This suggests that the pattern of HO formation retraces the ontogenetic steps that normally occur during intramembranous ossification. The authors also discuss the peculiar concomitance of HO formation and keloid development, speculating that, although they are different conditions localized in dissimilar regions, they might be hypothetically triggered by a common event, such as the release of factors likely issued during the coma status.
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http://dx.doi.org/10.1002/ca.20616DOI Listing
May 2008

Ovariectomy sensitizes rat cortical bone to whole-body vibration.

Calcif Tissue Int 2008 Apr 1;82(4):316-26. Epub 2008 Apr 1.

Bone Metabolic Unit, Scientific Institute San Raffaele, Via Olgettina 60, Milan 20132, Italy.

This study was designed to determine the modulatory effect of estrogen on mechanical stimulation in bone. Trabecular and cortical bone compartments of ovariectomized rats exposed to whole-body vibration of different amplitudes were evaluated by peripheral quantitative computed tomographic (pQCT) analysis and histomorphometry and compared to controls not exposed to vibration. Rats underwent whole-body vibration (20 minutes/day, 5 days/week) on a vibration platform for 2 months. The control rats were placed on the platform without vibration for the same time. We divided rats into six groups: a sham control (SHAM); a sham vibrated (SHAM-V) at 30 Hz, 0.6 g; a SHAM-V at 30 Hz, 3g; an ovariectomized control (OVX); an ovariectomized vibrated (OVX-V) at 30 Hz, 0.6 g; and an OVX-V at 30 Hz, 3g. In vivo, pQCT analyses of the tibiae were performed at the start of the experiment and after 4 and 8 weeks. After 8 weeks the tibiae were excised for histomorphometric and for in vitro pQCT analyses. In the SHAM-V group, vibration had no effect upon the different bone parameters. In the OVX-V group, vibration induced a significant increase compared to the OVX group of the cortical and medullary areas (P < 0.01) and of the periosteal (P < 0.01) and endosteal (P < 0.05) perimeters at the 3 g vibration. The strain strength index increased in the OVX-V group significantly (P < 0.01) at the higher vibration. The results showed that low-amplitude, high-frequency whole-body vibration is anabolic to bone in OVX animals. The osteogenic potential is limited to the modeling of the bone cortex and depends on the amplitude of the vibration.
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http://dx.doi.org/10.1007/s00223-008-9115-8DOI Listing
April 2008

Cartilage repair with osteochondral autografts in sheep: effect of biophysical stimulation with pulsed electromagnetic fields.

J Orthop Res 2008 May;26(5):631-42

Orthopaedic and Traumatologic Clinic, University of Pavia, IRCCS Policlinico S. Matteo, Pavia, Italy.

The effect of pulsed electromagnetic fields (PEMFs) on the integration of osteochondral autografts was evaluated in sheep. After osteochondral grafts were performed, the animals were treated with PEMFs for 6 h/day or sham-treated. Six animals were sacrificed at 1 month. Fourteen animals were treated for 2 months and sacrificed at 6 months. At 1 month, the osteogenic activity at the transplant-host subchondral bone interface was increased in PEMF-treated animals compared to controls. Articular cartilage was healthy in controls and stimulated animals. At 6 months, complete resorption was observed in four control grafts only. Cyst-like resorption areas were more frequent within the graft of sham-treated animals versus PEMF-treated. The average volume of the cysts was not significantly different between the two groups; nevertheless, analysis of the variance of the volumes demonstrated a significant difference. The histological score showed no significant differences between controls and stimulated animals, but the percentage of surface covered by fibrous tissue was higher in the control group than in the stimulated one. Interleukin-1 and tumor necrosis factor-alpha concentration in the synovial fluid was significantly lower, and transforming growth factor-beta1 was significantly higher, in PEMF-treated animals compared to controls. One month after osteochondral graft implantation, we observed larger bone formation in PEMF-treated grafts which favors early graft stabilization. In the long term, PEMF exposure limited the bone resorption in subchondral bone; furthermore, the cytokine profile in the synovial fluid was indicative of a more favorable articular environment for the graft.
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http://dx.doi.org/10.1002/jor.20530DOI Listing
May 2008

Effect of pulsed electromagnetic field stimulation on knee cartilage, subchondral and epyphiseal trabecular bone of aged Dunkin Hartley guinea pigs.

Biomed Pharmacother 2008 Dec 3;62(10):709-15. Epub 2007 Apr 3.

Laboratory of Experimental Surgery, Research Institute Codivilla-Putti, Rizzoli Orthopaedic Institute, Bologna, Italy.

It has been demonstrated that pulsed electromagnetic field (PEMF) stimulation has a chondroprotective effect on osteoarthritis (OA) progression in the knee joints of the 12-month-old guinea pigs. The aim of the present study was to discover whether the therapeutic efficacy of PEMFs was maintained in older animals also in more severe OA lesions. PEMFs were administered daily (6 h/day for 6 months) to 15-month-old guinea pigs. The knee joints (medial and lateral tibial plateaus, medial and lateral femoral condyles) were evaluated by means of a histological/histochemical Mankin modified by Carlsson grading score and histomorphometric measurements of cartilage thickness (CT), fibrillation index (FI), subchondral bone thickness (SBT) and epiphyseal bone microarchitecture (bone volume: BV/TV; trabecular thickness: Tb.Th; trabecular number: Tb.N; trabecular separation: Tb.SP). Periarticular knee bone was also evaluated with dual X-ray absorptiometry (DXA). PEMF stimulation significantly changed the progression of OA lesions in all examined knee areas. In the most affected area of the knee joint (medial tibial plateau), significant lower histochemical score (p<0.0005), FI (p<0.005), SBT (p<0.05), BV/TV (p<0.0005), Tb.Th (p<0.05) and Tb.N (p<0.05) were observed while CT (p<0.05) and Tb.Sp (p<0.0005) were significantly higher than in SHAM-treated animals. DXA confirmed the significantly higher bone density in SHAM-treated animals. Even in the presence of severe OA lesions PEMFs maintained a significant efficacy in reducing lesion progression.
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http://dx.doi.org/10.1016/j.biopha.2007.03.001DOI Listing
December 2008