Publications by authors named "Ruchun Dai"

19 Publications

  • Page 1 of 1

Serum exosomes from young rats improve the reduced osteogenic differentiation of BMSCs in aged rats with osteoporosis after fatigue loading in vivo.

Stem Cell Res Ther 2021 07 27;12(1):424. Epub 2021 Jul 27.

National Clinical Research Center for Metabolic Diseases, Institute of Metabolism and Endocrinology, Central South University, Hunan Provincial Key Laboratory of Metabolic Bone Diseases, and Department of Metabolism and Endocrinology, The Second Xiangya Hospital of Central South University, Changsha, Hunan, China.

Background: Osteoporosis is a major public health concern for the elderly population and is characterized by fatigue load resulting in bone microdamage. The ability of bone mesenchymal stem cells (BMSCs) to repair bone microdamage diminishes with age, and the accumulation of bone microdamage increases the risk of osteoporotic fracture. There is a lack of effective means to promote the repair of bone microdamage in aged patients with osteoporosis. Exosomes have been shown to be related to the osteogenic differentiation of BMSCs. Here, we aimed to evaluate the changes in the osteogenic differentiation capacity of BMSCs in aged osteoporotic rats after fatigue loading and the treatment potential of serum exosomes from young rats.

Methods: The tibias of six aged osteoporotic rats were subjected to fatigue loading in vivo for 2 weeks, and the bone microdamage, microstructures, and mechanical properties were assessed. Subsequently, BMSCs were extracted to evaluate their proliferation and osteogenic differentiation abilities. In addition, the BMSCs of aged osteoporotic rats after fatigue loading were treated with serum exosomes from young rats under osteogenic induction conditions, and the expression of osteogenic-related miRNAs was quantified. The osteogenetic effects of miRNA-19b-3p in exosomes and the possible target protein PTEN was detected.

Results: Obvious bone microdamage at the fatigue load stress point, the bone microstructure and biomechanical properties were not obviously changed. A decreased osteogenic differentiation ability of BMSCs was observed after fatigue loading, while serum exosomes from young rats highly expressing miRNA-19b-3p improved the decreased osteogenic differentiation ability of BMSCs. Transfection with miRNA-19b-3p mimic could promote osteoblastic differentiation of BMSCs and decreased the expression of PTEN. After transfection of miRNA-19b-3p inhibitor, the promotional effect of exosomes on bone differentiation was weakened. Treatment with transfected exosomes increased the expression of PTEN.

Conclusion: Serum exosomes derived from young rats can improve the decreased osteogenic differentiation ability of BMSCs in aged rats with osteoporosis after fatigue loading and can provide a new treatment strategy for the repair of bone microdamage and prevention of fractures.
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http://dx.doi.org/10.1186/s13287-021-02449-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8314589PMC
July 2021

Immunodominant regions prediction of nucleocapsid protein for SARS-CoV-2 early diagnosis: a bioinformatics and immunoinformatics study.

Pathog Glob Health 2020 12 16;114(8):463-470. Epub 2020 Nov 16.

Department of Microbiology and Immunology, University of Texas Health Science Center at San Antonio , San Antonio,TX, 7703 Floyd Curl Drive, 78229, USA.

COVID-19 caused by SARS-CoV-2 is sweeping the world and posing serious health problems. Rapid and accurate detection along with timely isolation is the key to control the epidemic. Nucleic acid test and antibody-detection have been applied in the diagnosis of COVID-19, while both have their limitations. Comparatively, direct detection of viral antigens in clinical specimens is highly valuable for the early diagnosis of SARS-CoV-2. The nucleocapsid (N) protein is one of the predominantly expressed proteins with high immunogenicity during the early stages of infection. Here, we applied multiple bioinformatics servers to forecast the potential immunodominant regions derived from the N protein of SARS-CoV-2. Since the high homology of N protein between SARS-CoV-2 and SARS-CoV, we attempted to leverage existing SARS-CoV immunological studies to develop SARS-CoV-2 diagnostic antibodies. Finally, N, N, and N were predicted to be the potential immunodominant regions, which contain both predicted linear B-cell epitopes and murine MHC class II binding epitopes. These three regions exhibited good surface accessibility and hydrophilicity. All were forecasted to be non-allergen and non-toxic. The final construct was built based on the bioinformatics analysis, which could help to develop an antigen-capture system for the early diagnosis of SARS-CoV-2.
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http://dx.doi.org/10.1080/20477724.2020.1838190DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7678408PMC
December 2020

Fetal bovine serum-derived exosomes regulate the adipogenic differentiation of human bone marrow mesenchymal stromal cells in a cross-species manner.

Differentiation 2020 Sep - Oct;115:11-21. Epub 2020 Jul 25.

Department of Metabolism and Endocrinology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, 410011, China; National Clinical Research Center for Metabolic Diseases, Changsha, Hunan, 410011, China; Hunan Provincial Key Laboratory of Metabolic Bone Diseases, Changsha, Hunan, 410011, China. Electronic address:

Fetal bovine serum (FBS) contains a large number of exosomes which may disturb the analysis of exosomes derived from cultured cells. We investigated the effect of FBS-derived exosomes (FBS-Exos) on the adipogenic differentiation of human bone marrow mesenchymal stromal cells (hBM-MSCs) and the underlying molecular mechanism. The uptake of FBS-Exos by hBM-MSCs could be detected by the laser confocal microscopy, and the treatment of exosomes resulted in the decreased lipid droplet formation and reduced expression of genes associated with adipogenic differentiation of hBM-MSCs. miR-1246 was identified as an abundant microRNA in FBS-Exos by public sequencing data identification and RT-qPCR validation. Moreover, miR-1246 overexpression in hBM-MSCs led to decreased adipogenic differentiation level, while miR-1246 knockdown in FBS-Exos attenuated the inhibitory effect on the adipogenic differentiation. Our results indicate that FBS-Exos inhibit the adipogenic differentiation of hBM-MSCs in a cross-species manner and miR-1246 transferred by FBS-Exos partly contributes to this effect.
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http://dx.doi.org/10.1016/j.diff.2020.06.004DOI Listing
August 2021

Bone mineral density spectrum in individuals with type 1 diabetes, latent autoimmune diabetes in adults, and type 2 diabetes.

Diabetes Metab Res Rev 2021 Mar 20;37(3):e3390. Epub 2020 Aug 20.

Department of Metabolism and Endocrinology, The Second Xiangya Hospital, Central South University, Changsha, China.

Objective: To assess bone mineral density (BMD) and associated clinical factors in patients with type 1 diabetes (T1D), latent autoimmune diabetes in adults (LADA), and type 2 diabetes (T2D) and in non-diabetic subjects.

Methods: Total 108 age-, sex-, disease duration-, and postmenopausal ratio-matched patients with T1D, LADA, and T2D each and 216 age-, sex-, and postmenopausal ratio-matched non-diabetic controls. Anthropometric, biochemical, and BMD data were collected and analysed.

Results: BMD of total hip and lumbar spine of individuals in the LADA group was lower than those in the T2D and control groups but higher than those in the T1D group. After adjusting for body mass index (BMI), a significant difference in BMD in the lumbar spine was seen between groups. After adjustment for smoking, BMI, 25-(OH) vitamin D, calcium, haemoglobin A1c, and diabetic complication scores, BMD values of patients in LADA group were not significantly different from those of patients in T1D and T2D groups. Multiple stepwise regression analysis showed that BMD was (a) positively associated with weight and C-peptide, and negatively associated with age in patients with diabetes, (b) positively associated with C-peptide in the T1D and LADA groups. The proportion of patients with osteoporosis in the T1D, LADA, T2D, and control groups was 55.6%, 45.4%, 34.3%, and 26.9%, respectively.

Conclusions: BMD values in T1D, LADA, and T2D were in an increasing order of mention. Patients with autoimmune diabetes were more susceptible to osteoporosis. A lower C-peptide level may be responsible for decreased BMD in individuals with autoimmune diabetes.
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http://dx.doi.org/10.1002/dmrr.3390DOI Listing
March 2021

Microstructural properties of trabecular bone autografts: comparison of men and women with and without osteoporosis.

Arch Osteoporos 2018 03 5;13(1):18. Epub 2018 Mar 5.

Department of Endocrinology and Metabolism, Hunan Provincial Key Laboratory of Metabolic Bone Diseases, National Clinical Research Center for Metabolic Disease, The Second XiangYa Hospital, Central South University, 139 Renmin Middle Road, Changsha, 410011, China.

The microstructure of autologous bone grafts from men over 50 years old and postmenopausal women undergoing spinal fusion were evaluated using micro-CT. We demonstrated postmenopausal women, especially those with osteoporosis (OP) presented more serious microarchitectural deterioration of bone grafts.

Purpose: This study was undertaken to determine microstructural properties of cancellous bone used as autologous bone grafts from osteoporosis patients undergoing lumbar fusion by comparing microstructural indices to controls.

Methods: Cancellous bone specimens from spinous processes were obtained from 41 postmenopausal women (osteoporosis women, n = 19; controls, n = 22) and 26 men over 50 years old (osteoporosis men, n = 8; controls, n = 18) during lumbar fusion surgery. The microstructural parameters were measured using micro-CT.

Results: Significant difference in bone volume fraction (BV/TV), specific bone surface (BS/BV), trabecular thickness (Tb.Th), and structure model index (SMI) value existed between postmenopausal women with OP and controls. Significant difference in trabecular number (Tb.N) existed between men over 50 years old with OP and controls. Postmenopausal women exhibited lower BV/TV, Tb.Th, and higher SMI value than men over 50 years old. Postmenopausal women with OP exhibited lower BV/TV, Tb.Th, and higher BS/BV than men over 50 years old with OP.

Conclusions: Post-menopausal women and older men with OP have worse bone quality in autografts than non-osteoporotic men and women. Postmenopausal women with OP presented serious microarchitectural deterioration in older population.
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http://dx.doi.org/10.1007/s11657-018-0422-zDOI Listing
March 2018

Fulminant type 1 diabetes caused by peginterferon α-2a therapy in hepatitis C.

J Diabetes 2018 May 5;10(5):419-420. Epub 2018 Feb 5.

Department of Metabolism and Endocrinology, Second Xiangya Hospital and Diabetes Center, Institute of Metabolism and Endocrinology, Central South University, Changsha, China.

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http://dx.doi.org/10.1111/1753-0407.12636DOI Listing
May 2018

Micro/Nanostructures and Mechanical Properties of Trabecular Bone in Ovariectomized Rats.

Int J Endocrinol 2015 27;2015:252503. Epub 2015 Jul 27.

Comprehensive Cancer Center and Urology, University of Michigan, E Medical Center Drive, Ann Arbor, MI 48109, USA ; Research & Development and Radiology, VA Southern Nevada Healthcare System, 6900 N. Pecos Road, North Las Vegas, NV 89086, USA.

Bone mechanical properties encompass both geometric and material factors, while the effects of estrogen deficiency on the material and structural characteristics of bone at micro- to nanoscales are still obscure. We performed a series of combined methodological experiments, including nanoindentation assessment of intrinsic material properties, atomic force microscopy (AFM) characterization of trabecular (Tb) nanostructure, and Tb microarchitecture and 2D BMD. At 15 weeks after surgery, we found significantly less Tb bone mineral density (BMD) at organ (-27%) and at tissue level (-12%), Tb bone volume fraction (-29%), Tb thickness (-14%), and Tb number (-17%) in ovariectomy (OVX) rats than in sham operated (SHAM) rats, while the structure model index (+91%) and Tb separation (+19%) became significantly greater. AFM images showed lower roughness Tb surfaces with loosely packed large nodular structures and less compacted interfibrillar space in OVX than in SHAM. However, no statistically significant changes were in the Tb intrinsic material properties-nanoindentation hardness, elastic modulus, and plastic deformation-nanoindentation depths, and residual areas. Therefore, estrogen deprivation results in a dramatic deterioration in Tb micro/nanoarchitectures, 3D volumetric BMD at both organ and tissue levels, and 2D BMD, but not in the nanomechanical properties of the trabeculae per se.
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http://dx.doi.org/10.1155/2015/252503DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4530249PMC
August 2015

Association of microstructural and mechanical properties of cancellous bone and their fracture risk assessment tool scores.

Int J Clin Exp Med 2015 15;8(3):3956-64. Epub 2015 Mar 15.

Institute of Metabolism and Endocrinology, The Second Xiangya Hospital, Central South University 139 Renmin-Zhong Road, Changsha 410011, Hunan, China.

This study is to investigate the association between fracture probabilities determined by using the fracture risk assessment tool (FRAX) and the microstructure and mechanical properties of femoral bone trabecula in osteoporosis (OP) and osteoarthritis (OA) patients with hip replacements. By using FRAX, we evaluated fracture risks of the 102 patients with bone replacements. Using micro CT scanning, we obtained the analysis parameters of microstructural properties of cancellous bone. Through morphometric observations, fatigue tests and compression tests, we obtained parameters of mechanical properties of cancellous bones. Relevant Pearson analysis was performed to investigate the association between the fracture probability and the microstructure and mechanical properties of femoral bone trabecula in patients. Fifteen risk factors in FRAX were compared between OP and OA patients. FRAX hip fracture risk score and major osteoporotic in OP and OA patients were significantly different. FRAX was associated with tissue bone mineral density and volumetric bone mineral density. Our study suggests that the probabilities of major osteoporotic and hip fracture using FRAX is associated with bone mass but not with micro bone quality.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4443131PMC
June 2015

[Effect of methylprednisolone on bone mass, microarchitecture and microdamage in cortical bone of ulna in rats].

Zhong Nan Da Xue Xue Bao Yi Xue Ban 2015 Jan;40(1):25-30

Deparment of Endocrinology, People's Hospital of Hainan, Haikou 570311, China.

Objective: To explore the effect of methylprednisolone on bone mass, microarchitecture and microdamage in cortical bone of ulna in rats.

Methods: Twenty female Sprague-Dawley rats (3.5 months old) were randomly assigned to two groups: a treatment group and a control group (n=10 per group). The treatment group was subcutaneously injected with methylprednisolone 3.5 mg/(kg.d) while the control group was subcutaneously injected with same volume of vehicle (saline). Rats were sacrificed at 9 weeks after the treatments. Before the sacrifice, the body weight and total bone mineral density (BMD) were measured. The right forelimb was separated through humeral shoulder and then single axial fatigue loading was performed on the right ulna. After fatigue load, the middle ulna section was bulkstained in basic fuchsin. Bone histomorphometry and microdamage analysis were performed on the middle ulna section.

Results: Compared with the control group, the body weight, total bone BMD and ulnas BMD in the treatment group were decreased by 15%, 6.4% and 4.3% respectively (all P<0.05); the ulna inner perimeter and marrow area in the treatment group were increased by 23.3% and 32%, respectively (both P<0.05), while the outer perimeter were decreased by 3.1% (P>0.05). There was no significant difference in the cortical and total area between the 2 groups (both P>0.05). The number of microcrack, microcrack density and microcrack surface density in the treatment group were increased by 43%, 48% and 50%, respectively, compared with those in the control group (all P<0.05), but there was no significant difference in the mean length of microcrack between the 2 groups (P>0.05).

Conclusion: Methylprednisolone can significantly induce the bone loss and the deterioration of microarchitecture and microdamage in ulna of rats.
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http://dx.doi.org/10.11817/j.issn.1672-7347.2015.01.005DOI Listing
January 2015

Avascular necrosis of the femoral head due to the bilateral injection of heroin into the femoral vein: A case report.

Exp Ther Med 2013 Oct 26;6(4):1041-1043. Epub 2013 Jul 26.

Department of Orthopedics, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, P.R. China.

In this study, we report a case of avascular necrosis of the femoral head (ANFH) caused by the bilateral intravenous injection of heroin into the femoral vein. The patient had not used steroids, did not smoke and did not drink excessively. The patient did not present with any systemic diseases that may cause ANFH. ANFH often causes changes to the bone mass of the femoral head, particularly, the weight-bearing bone region. Imaging examination revealed that in addition to the bilateral hip joints, widespread changes to the bone mass existed in the peripheral area, where phlebitis and disseminated thrombosis had been caused by the injection of heroin. These results suggest that this ANFH case was related to the injection of heroin. This case is different from other cases of ANFH which have been caused by steroids and other factors, including smoking, alcohol intake and cytotoxic agents.
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http://dx.doi.org/10.3892/etm.2013.1236DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3797317PMC
October 2013

Self-repair of rat cortical bone microdamage after fatigue loading in vivo.

Int J Endocrinol 2013 10;2013:321074. Epub 2013 Apr 10.

Institute of Metabolism and Endocrinology, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, China.

Bone microdamage can be repaired through bone remodeling induced by loading. In this study, a loading device was developed for improved efficiency and the self-repair process of bone microdamage was studied in ovariectomized rats. First, four-point bending fixtures capable of holding two live rats simultaneously were designed. Rats were loaded and subjected to a sinusoidal wave for 10,000 cycles. They were then divided into four groups to evaluate time points from 1 to 4 weeks in the microdamage repair process. The loaded right ulna was used for microdamage parameter analysis, and the loaded right radius was tested for mechanical properties. In all groups, microdamage consisted primarily of microcracks, which were observed in bone surrounding the force-bearing point. The values of the microdamage parameters were significantly lower at 3 weeks than at 2 weeks. However, none of the differences in mechanical properties between any four groups were statistically significant. This study shows that the improved application of loading in the form of bending for double-rat simultaneous administration was practical and efficient. These results suggest that microdamage was repaired between 2 weeks to 3 weeks after fatigue damage and microdamage is a more sensitive index of bone quality than mechanical properties.
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http://dx.doi.org/10.1155/2013/321074DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3639633PMC
May 2013

Effects of genistein on neuronal apoptosis, and expression of Bcl-2 and Bax proteins in the hippocampus of ovariectomized rats.

Neural Regen Res 2012 Dec;7(36):2874-81

Department of Neurology, the Second Xiangya Hospital, Central South University, Changsha 410011, Hunan Province, China.

Genistein is one of several isoflavones that has a structure similar to 17β-estradiol, has a strong antioxidant effect, and a high affinity to estrogen receptors. At 15 weeks after ovariectomy, the expression of Bcl-2 in the hippocampus of rats decreased and Bax expression increased, with an obvious upregulation of apoptosis. However, intraperitoneal injection of genistein or 17β-estradiol for 15 consecutive weeks from the second day after operation upregulated Bcl-2 protein expression, downregulated Bax protein expression, and attenuated hippocampal neuron apoptosis. Our experimental findings indicate that long-term intervention with genistein can lead to a decrease in apoptosis in hippocampal neurons following ovariectomy, upregulate the expression of Bcl-2, and downregulate the expression of Bax. In addition, genistein and 17β-estradiol play equal anti-apoptotic and neuroprotective roles.
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http://dx.doi.org/10.3969/j.issn.1673-5374.2012.36.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4190945PMC
December 2012

Problem-, team- and evidence-based learning.

Med Educ 2012 Nov;46(11):1102-3

Institute of Metabolism and Endocrinology, Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, China.

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http://dx.doi.org/10.1111/medu.12033DOI Listing
November 2012

Relationship of body composition with prevalence of osteoporosis in central south Chinese postmenopausal women.

Clin Endocrinol (Oxf) 2011 Mar;74(3):319-24

Institute of Metabolism and Endocrinology, the Second Xiang-Ya Hospital, Central South University, Changsha, China.

Objectives: To elucidate the relationship between body composition and bone mineral density (BMD) and the prevalence of osteoporosis in central south Chinese postmenopausal women.

Methods: A cross-sectional study was conducted on 954 healthy central southern Chinese postmenopausal women, aged 50-82. Total body, lumbar spine and left femur BMD and total body soft tissue composition were measured by dual X-ray absorptiometry.

Results: Among the study population, 578 (60.5%) subjects were without osteoporosis and 376 (39.4%) subjects were osteoporotic. The osteoporotic women were older, shorter and thinner, had an earlier age at menopause, a lower BMD and bone mineral content (BMC) of the total body and at different sites, and had lower body mass and body mass components than the women without osteoporosis. Both fat mass and lean mass were positively correlated with age at menopause, height, weight, body mass index (BMI) and BMD at all sites. Fat mass and lean mass were also inversely correlated with age and years since menopause (P<0.05). After controlling for age, age at menopause and height, both fat mass and lean mass were positively correlated with BMD at the lumbar(1-4) spine, the femoral neck and the total hip. Fat mass was the most significant determinant of BMD at the lumbar(1-4) spine with a higher R(2) change and a partial R(2) compared with that of lean mass, while lean mass had more impact on the total hip values. Either a fat mass below 18.4 kg or a lean mass below 33.9 kg was correlated with a higher prevalence of osteoporosis at the lumbar spine or total hip.

Conclusions: In central south Chinese postmenopausal women, both fat mass and lean mass are correlated with BMD at the lumbar spine and hip. Fat mass was the most significant determinant of BMD at the lumbar spine, while lean mass had more impact on the total hip value. Both lower values of fat mass and lean mass are related to a higher prevalence of osteoporosis at either the lumbar spine or the total hip. Thus, it is important to maintain a reasonable body weight to balance bone health and other metabolic disorders.
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http://dx.doi.org/10.1111/j.1365-2265.2010.03941.xDOI Listing
March 2011

Experimental study of damage and fracture of cancellous bone using a digital speckle correlation method.

J Biomed Opt 2008 May-Jun;13(3):034026

Tsinghua University, Department of Engineering Mechanics, Beijing 100084, China.

Cancellous bone is a widespread structure in a creatural body, for instance, in the femoral head and spondyle. The damage evolution and crack growth of cattle cancellous bone were studied under three-point-bending load conditions. A series of speckle images with deformation information surrounding the crack tip were recorded, and the full-field displacement distributions were obtained at different loading levels by means of digital speckle correlation method (DSCM). Characterizations of the damage deformation and fracture of cancellous bone were analyzed. These results provide some useful information for studying the fracture behavior of cancellous bone.
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http://dx.doi.org/10.1117/1.2928126DOI Listing
September 2008

Effects of genistein on vertebral trabecular bone microstructure, bone mineral density, microcracks, osteocyte density, and bone strength in ovariectomized rats.

J Bone Miner Metab 2008 4;26(4):342-9. Epub 2008 Jul 4.

Institute of Metabolism and Endocrinology, Second Xiang-Ya Hospital, Central South University, 139 Renmin-Zhong Rd, Changsha, 410011 Hunan, China.

Until now, the effects of phytoestrogen on bone in both women and ovarian hormone-deficient animal models of osteoporosis have remained uncertain. We have aimed here to investigate the effect of genistein (GEN) on trabecular bone quality in ovariectomized (OVX) rats. Forty 7-month-old female Sprague-Dawley rats were randomly divided into the following four groups: OVX, sham-operated (SHAM), treated with 17beta-estradiol (EST, 10 microg x kg(-1) x day(-1)), and GEN (5 mg x kg(-1) x day(-1)). At 15 weeks postoperation, the compressive test was performed on the L5 vertebral body; additionally, microcomputed tomography (micro-CT) assessment was performed to estimate the bone mineral density (BMD) and microstructure parameters of the L6 vertebral body. After fatigue damage testing, the L6 vertebral body was bulk-stained in 1% basic fuchsin and embedded in methylmethacrylate. The L4 vertebral body was embedded in methylmethacrylate for dynamic histomorphometry analysis without staining. Mounted bone slices were used to measure microcrack parameters, empty osteocyte lacuna density (e.Lc.Dn), and osteocyte density (Ot.N/T.Ar). Maximum loading (ML) and Ot.N/T.Ar were significantly lower in the OVX group than in the other groups. E.Lc.Dn was significantly decreased in GEN and EST groups compared to the OVX group. ML was significantly decreased in the GEN group compared to the SHAM group. Microcrack density, microcrack surface density, and microcrack length were significantly increased in the OVX group compared to the other groups. Mineral apposition rate was significantly decreased in the OVX group compared to the SHAM and GEN groups. Bone formation rate was significantly decreased in the OVX group compared to other groups. There were no significant differences with regard to mineralizing surface among the four groups. Volumetric BMD at organ was significantly lower in OVX, EST, and GEN groups than in the SHAM group. Bone mineral content was significantly lower in the OVX group than in the SHAM group. Bone volume fraction and trabecular number were significantly decreased in OVX, EST, and GEN groups compared to the SHAM group. Structure model index was significantly lower in the SHAM group than in OVX, EST, and GEN groups. Trabecular separation was significantly increased in the OVX group compared to SHAM and EST groups. There were no significant differences with regard to the trabecular thickness (Tb,Th) between SHAM, GEN, and OVX groups. Tb.Th was significantly lower in the EST group than in the SHAM group. Connectivity density (Conn.D) was significantly lower in the OVX group than in SHAM and GEN groups, and Conn. D was significantly lower in the EST group than in GEN. In conclusion, the present study demonstrates that GEN preserved the biomechanical quality of the trabecular bone regardless of the microstructure and BMD.
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http://dx.doi.org/10.1007/s00774-007-0830-4DOI Listing
September 2008

Comparison of the effects of genistein and zoledronic acid on the bone loss in OPG-deficient mice.

Bone 2008 May 8;42(5):950-9. Epub 2008 Feb 8.

Institute of Metabolism and Endocrinology, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, PR China.

Unlabelled: Using osteoprotegerin (OPG)-knockout mice, we demonstrated that in vivo the effects of both genistein and 17beta-estradiol (E2) on bone metabolism were completely abolished. In contrast, zoledronic acid could effectively suppress bone resorption and prevent bone loss.

Introduction: The anti-resorptive effects of E2 on bone metabolism are considered to be mediated via modulation of the osteoblast-derived paracrine factor OPG. Recently, the phytoestrogen genistein was found to suppress bone resorption by enhancing osteoblastic production of OPG. However, the mechanism underlying the in vivo effects of E2 and genistein on bone is not entirely understood, and a central question in this regard is whether E2 regulates bone metabolism via an OPG-dependent pathway.

Methods: After mating heterozygous (OPG+/-) mice, homozygous (OPG-/-) and wild-type (WT) with a mixed C57BL/6J x 129/SV background were obtained. The study involved 6-week-old female OPG-/- (n=40) and WT mice (n=8). The OPG-/- mice were randomly divided into 5 groups (n=8 per group) as follows: (1) genistein-treated mice (Gen) that were subcutaneously injected with genistein at a maximal dose (0.8 mg/day); (2) E2-treated mice (E2) that were subcutaneously injected with E2 at a dose (0.03 microg/day); (3) DMSO control mice (DMSO) that were subcutaneously injected with a mixture of dimethylsulfoxide (DMSO) and polyethyleneglycol-300; (4) zoledronic acid-treated mice (Zol) that were subcutaneously injected with zoledronic acid at a dose of (150 microg/kg) twice per week; and (5) H2O control mice that were subcutaneously injected with sterilized water twice per week. The doses of genistein, estrogen and zoledronic acid were selected based on the results of dose-response effect of agents on bone versus uterus in OPG-/- mice. The mice were sacrificed 6 weeks after this intervention. The microarchitecture of the trabecular and cortical bone was assessed by performing microcomputed tomography (micro-CT) for the right proximal tibia. The bone mineral density (BMD) of the left femur was measured by dual-energy X-ray absorptiometry (DXA). The biomechanical parameters of the right femur were determined by a three-point bend testing. Serum levels of bone alkaline phosphatase (B-ALP), tartarate-resistant acid phosphatase-5b (TRACP-5b), and receptor activator of nuclear factor kappaB ligand (RANKL) were determined by performing ELISA.

Results: DXA analysis revealed that the total BMD of the femur was not significantly altered in the Gen, E2, H2O, and DMSO groups. The three-point bending test revealed no significant differences in the biomechanical parameters, including ultimate loading, ultimate stress, stiff index, and elastic modulus, and micro-CT analysis revealed that the microarchitectural parameters of the trabecular bone (vBMD, tBMD, BVF, BSF, SMI, Tb.N, Conn.D, Tb.Sp, and Tb.Th) and cortical bone (Ct.Th, Mm, In.Pm, Ot.Pm, Ma.Ar, Ct.Ar, Tt.Ar, Ct.BMD, and Ct.BMC) did not differ among the groups. Genistein and E2 treatment did not alter the serum TRACP-5b, B-ALP, or RANKL levels. However, in addition to increasing the bone mass, zoledronic acid could effectively improve biomechanical parameters and could completely prevent deterioration of the bone architecture in the OPG-/- mice.

Conclusions: The effects of genistein and E2 on bone metabolism in vivo were lost completely in OPG-deficient mice, suggesting that the effect of these agents on bone metabolism seems to be entirely dependent on OPG. In contrast, zoledronic acid could effectively suppress bone resorption and completely prevent the bone loss in the OPG-/- mice--an effect that is likely to be independent of the OPG pathway.
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http://dx.doi.org/10.1016/j.bone.2008.01.010DOI Listing
May 2008

Effects of 17beta-estradiol on the expression of IL-6, IL-11 and NF-kappaB in human MG-63 osteoblast-like cell line.

J Huazhong Univ Sci Technolog Med Sci 2006 ;26(1):53-8

Department of Gerontism, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.

In order to characterize the effects of 17beta-estradiol (17beta-E2) on the expression of IL-6, IL-11 and NF-kappaB in the human MG-63 osteoblast-like cell line, the expression of IL-6 was detected by RT-PCR, Northern blot and Western blot. The expression of IL-11 was determined by RT-PCR, and NF-kappaB by Western blot. The results showed that 17beta-E2 down-regulated the expression of IL-6 mRNA and protein, IL-11 mRNA and NF-kappaB protein in MG-63 cells. It was suggested that the expression of NF-kappaB, IL-6 and IL-11 in MG-63 cells could be suppressed by 17beta-E2, and this might lend support to estrogen replacement therapy in postmenopausal women.
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http://dx.doi.org/10.1007/BF02828038DOI Listing
October 2006

[Manufacture and application of SL-2000 bone fatigue damage testing device].

Sheng Wu Yi Xue Gong Cheng Xue Za Zhi 2006 Feb;23(1):192-5

Institute of Metabolism and Endocrinology, The Second Xiang-Ya Hospital, Central South University, Changsha 410011 China.

Having manufactured the bone fatigue damage testing device SL-2000, we applied it to research on bone fatigue damage and on the bone microdamage which can indicate bone biomechanical property. According to the general principle of industry fatigue machine and bone fatigue test, the strength, frequency and times of loading, temperature and degree of wetness were controlled in the SL-2000 Device for making the experiment condition stable. After the fatigue damage to SD rats' vertebrae, the models of bone microdamage in SD rat were established. 0-200 N of strength, 0-10 Hz frequency, and 0-999999 times of loading, ambient temperature 50 degrees C experiment, and approximately 99% of the ambient degree of wetness could be adjusted continuously. Three kinds of microdamage such as microcrack, cross-hatch staining, and diffuse staining were observed in the SD rats' vertebrae fatigue damaged by the device. The microcrack density was 19.76+/-15.05 #/mm2, the microcrack length was 36. 74+/-11. 51 microm, and the area ratio of diffuse staining was 0.4117%. Therefore the device is suitable for bone fatigue damage test and for establishment of the model of bone microdamage.
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February 2006
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