230 results match your criteria Bone research[Journal]


Exosomes: roles and therapeutic potential in osteoarthritis.

Bone Res 2020 19;8:25. Epub 2020 Jun 19.

Department of Wound Repair and Rehabilitation Medicine, Center of Bone Metabolism and Repair, Laboratory for Prevention and Rehabilitation of Training Injuries, State Key Laboratory of Trauma, Burns and Combined Injury, Trauma Center, Research Institute of Surgery, Daping Hospital, Army Medical University, Chongqing, China.

Exosomes participate in many physiological and pathological processes by regulating cell-cell communication, which are involved in numerous diseases, including osteoarthritis (OA). Exosomes are detectable in the human articular cavity and were observed to change with OA progression. Several joint cells, including chondrocytes, synovial fibroblasts, osteoblasts, and tenocytes, can produce and secrete exosomes that influence the biological effects of targeted cells. Read More

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http://dx.doi.org/10.1038/s41413-020-0100-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7305215PMC

A variant in with a selective IL-11 signaling defect in human and mouse.

Bone Res 2020 11;8:24. Epub 2020 Jun 11.

Translational Gastroenterology Unit, John Radcliffe Hospital, University of Oxford, Oxford, UK.

The GP130 cytokine receptor subunit encoded by is the shared receptor for ten cytokines of the IL-6 family. We describe a homozygous non-synonymous variant in (p.R281Q) in a patient with craniosynostosis and retained deciduous teeth. Read More

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http://dx.doi.org/10.1038/s41413-020-0098-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7289831PMC

Molecular mechanosensors in osteocytes.

Bone Res 2020 8;8:23. Epub 2020 Jun 8.

Guangdong Provincial Key Laboratory of Cell Microenvironment and Disease Research, Shenzhen Key Laboratory of Cell Microenvironment, and School of Medicine, Southern University of Science and Technology, Shenzhen, 518055 China.

Osteocytes, the most abundant and long-lived cells in bone, are the master regulators of bone remodeling. In addition to their functions in endocrine regulation and calcium and phosphate metabolism, osteocytes are the major responsive cells in force adaptation due to mechanical stimulation. Mechanically induced bone formation and adaptation, disuse-induced bone loss and skeletal fragility are mediated by osteocytes, which sense local mechanical cues and respond to these cues in both direct and indirect ways. Read More

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http://dx.doi.org/10.1038/s41413-020-0099-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7280204PMC

Comparison of skeletal and soft tissue pericytes identifies CXCR4 bone forming mural cells in human tissues.

Bone Res 2020 22;8:22. Epub 2020 May 22.

Departments of Pathology, Johns Hopkins University, Baltimore, 21205 MD USA.

Human osteogenic progenitors are not precisely defined, being primarily studied as heterogeneous multipotent cell populations and termed mesenchymal stem cells (MSCs). Notably, select human pericytes can develop into bone-forming osteoblasts. Here, we sought to define the differentiation potential of CD146 human pericytes from skeletal and soft tissue sources, with the underlying goal of defining cell surface markers that typify an osteoblastogenic pericyte. Read More

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http://dx.doi.org/10.1038/s41413-020-0097-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7244476PMC

Osteogenesis imperfecta mutations in plastin 3 lead to impaired calcium regulation of actin bundling.

Bone Res 2020 22;8:21. Epub 2020 May 22.

Department of Chemistry and Biochemistry, The Ohio State University, Columbus, OH 43210 USA.

Mutations in actin-bundling protein plastin 3 (PLS3) emerged as a cause of congenital osteoporosis, but neither the role of PLS3 in bone development nor the mechanisms underlying PLS3-dependent osteoporosis are understood. Of the over 20 identified osteoporosis-linked PLS3 mutations, we investigated all five that are expected to produce full-length protein. One of the mutations distorted an actin-binding loop in the second actin-binding domain of PLS3 and abolished F-actin bundling as revealed by cryo-EM reconstruction and protein interaction assays. Read More

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http://dx.doi.org/10.1038/s41413-020-0095-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7244493PMC

Osteoblasts are inherently programmed to repel sensory innervation.

Bone Res 2020 13;8:20. Epub 2020 May 13.

1Instituto de Investigação e Inovação em Saúde (i3S), Universidade do Porto, 4200-135 Porto, Portugal.

Tissue innervation is a complex process controlled by the expression profile of signaling molecules secreted by tissue-resident cells that dictate the growth and guidance of axons. Sensory innervation is part of the neuronal network of the bone tissue with a defined spatiotemporal occurrence during bone development. Yet, the current understanding of the mechanisms regulating the map of sensory innervation in the bone tissue is still limited. Read More

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http://dx.doi.org/10.1038/s41413-020-0096-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7220946PMC

Ionomycin ameliorates hypophosphatasia via rescuing alkaline phosphatase deficiency-mediated L-type Ca channel internalization in mesenchymal stem cells.

Bone Res 2020 26;8:19. Epub 2020 Apr 26.

1State Key Laboratory of Military Stomatology & National Clinical Research Center for Oral Diseases & Shaanxi International Joint Research Center for Oral Diseases, Center for Tissue Engineering, School of Stomatology, The Fourth Military Medical University, Xi'an, 710032 Shaanxi China.

The loss-of-function mutations in the ALPL result in hypophosphatasia (HPP), an inborn metabolic disorder that causes skeletal mineralization defects. In adults, the main clinical features are early loss of primary or secondary teeth, osteoporosis, bone pain, chondrocalcinosis, and fractures. However, guidelines for the treatment of adults with HPP are not available. Read More

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http://dx.doi.org/10.1038/s41413-020-0090-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7183511PMC

uPAR antibody (huATN-658) and Zometa reduce breast cancer growth and skeletal lesions.

Bone Res 2020 17;8:18. Epub 2020 Apr 17.

1Department of Medicine, McGill University, Montréal, QC H4A3J1 Canada.

Urokinase plasminogen activator receptor (uPAR) is implicated in tumor growth and metastasis due to its ability to activate latent growth factors, proteases, and different oncogenic signaling pathways upon binding to different ligands. Elevated uPAR expression is correlated with the increased aggressiveness of cancer cells, which led to its credentialing as an attractive diagnostic and therapeutic target in advanced solid cancer. Here, we examine the antitumor effects of a humanized anti-uPAR antibody (huATN-658) alone and in combination with the approved bisphosphonate Zometa (Zoledronic acid) on skeletal lesion through a series of studies in vitro and in vivo. Read More

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http://dx.doi.org/10.1038/s41413-020-0094-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7165173PMC

Correction: Humanized bone facilitates prostate cancer metastasis and recapitulates therapeutic effects of Zoledronic acid in vivo.

Bone Res 2020;8:17. Epub 2020 Apr 3.

1Centre in Regenerative Medicine, Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Australia.

[This corrects the article DOI: 10.1038/s41413-019-0072-9.]. Read More

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http://dx.doi.org/10.1038/s41413-020-0092-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7118404PMC

Dystrophic calcification and heterotopic ossification in fibrocartilaginous tissues of the spine in diffuse idiopathic skeletal hyperostosis (DISH).

Bone Res 2020 2;8:16. Epub 2020 Apr 2.

2Bone and Joint Institute, The University of Western Ontario, London, ON N6G 2V4 Canada.

Diffuse idiopathic skeletal hyperostosis (DISH) is a prevalent noninflammatory spondyloarthropathy characterized by ectopic mineral formation along the anterolateral aspect of the vertebral column, yet little is known about its underlying pathogenesis. Our objective was to evaluate the histopathological features and composition of ectopic mineral within spinal tissues affected by DISH in humans. Thoracic spine segments from six embalmed cadaveric donors (one female and five males; median age 82 years) meeting the radiographic diagnostic criteria for DISH were evaluated using radiological, histological, and physical analyses. Read More

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http://dx.doi.org/10.1038/s41413-020-0091-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7118090PMC

Correction to: AFF1 and AFF4 differentially regulate the osteogenic differentiation of human MSCs.

Bone Res 2020 31;8:15. Epub 2020 Mar 31.

1State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China.

[This corrects the article DOI: 10.1038/boneres.2017. Read More

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http://dx.doi.org/10.1038/s41413-020-0093-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7109067PMC

Mitigating osteonecrosis of the jaw (ONJ) through preventive dental care and understanding of risk factors.

Bone Res 2020 11;8:14. Epub 2020 Mar 11.

1National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD USA.

It is well established that alterations in phosphate metabolism have a profound effect on hard and soft tissues of the oral cavity. The present-day clinical form of osteonecrosis of the jaw (ONJ) was preceded by phosphorus necrosis of the jaw, ca. 1860. Read More

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http://dx.doi.org/10.1038/s41413-020-0088-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7064532PMC

The cartilage matrisome in adolescent idiopathic scoliosis.

Bone Res 2020 9;8:13. Epub 2020 Mar 9.

5Department of Developmental Biology, Washington University School of Medicine, St. Louis, MO 63110 USA.

The human spinal column is a dynamic, segmented, bony, and cartilaginous structure that protects the neurologic system and simultaneously provides balance and flexibility. Children with developmental disorders that affect the patterning or shape of the spine can be at risk of neurologic and other physiologic dysfunctions. The most common developmental disorder of the spine is scoliosis, a lateral deformity in the shape of the spinal column. Read More

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http://dx.doi.org/10.1038/s41413-020-0089-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7062733PMC

ZBP1 (DAI/DLM-1) promotes osteogenic differentiation while inhibiting adipogenic differentiation in mesenchymal stem cells through a positive feedback loop of Wnt/β-catenin signaling.

Bone Res 2020 5;8:12. Epub 2020 Mar 5.

1State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Chinese Academy of Medical Sciences Research Unit of Oral Carcinogenesis and Management, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan 610041 PR China.

The lineage specification of mesenchymal stem/stromal cells (MSCs) is tightly regulated by a wide range of factors. Recently, the versatile functions of ZBP1 (also known as DAI or DLM-1) have been reported in the blood circulation and immune systems. However, the biological function of ZBP1 during the lineage specification of MSCs is still unknown. Read More

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http://dx.doi.org/10.1038/s41413-020-0085-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7058036PMC

Osteoclasts are not a source of SLIT3.

Bone Res 2020 19;8:11. Epub 2020 Feb 19.

4Department of Pathology and Laboratory Medicine, Weill Cornell Medical College, Cornell University, New York, NY USA.

The axon guidance cue SLIT3 was identified as an osteoanabolic agent in two recent reports. However, these reports conflict in their nomination of osteoblasts versus osteoclasts as the key producers of skeletal SLIT3 and additionally offer conflicting data on the effects of SLIT3 on osteoclastogenesis. Here, aiming to address this discrepancy, we found no observable SLIT3 expression during human or mouse osteoclastogenesis and the only modest SLIT3-mediated effects on osteoclast differentiation. Read More

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http://dx.doi.org/10.1038/s41413-020-0086-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7031526PMC
February 2020

Melatonin alleviates intervertebral disc degeneration by disrupting the IL-1β/NF-κB-NLRP3 inflammasome positive feedback loop.

Bone Res 2020 18;8:10. Epub 2020 Feb 18.

1Department of Spine Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510080 China.

The inflammatory response is induced by the overexpression of inflammatory cytokines, mainly interleukin (IL)-1β, and is one of the main causes of intervertebral disc degeneration (IVDD). NLR pyrin domain containing 3 (NLRP3) inflammasome activation is an important source of IL-1β. As an anti-inflammatory neuroendocrine hormone, melatonin plays various roles in different pathophysiological conditions. Read More

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http://dx.doi.org/10.1038/s41413-020-0087-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7028926PMC
February 2020

Skeletal loading regulates breast cancer-associated osteolysis in a loading intensity-dependent fashion.

Bone Res 2020 14;8. Epub 2020 Feb 14.

1Department of Pharmacology, School of Pharmacy, Harbin Medical University, Harbin, 150081 China.

Osteocytes are mechanosensitive bone cells, but little is known about their effects on tumor cells in response to mechanical stimulation. We treated breast cancer cells with osteocyte-derived conditioned medium (CM) and fluid flow-treated conditioned medium (FFCM) with 0.25 Pa and 1 Pa shear stress. Read More

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http://dx.doi.org/10.1038/s41413-020-0083-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7021802PMC
February 2020

Long-term bone and lung consequences associated with hospital-acquired severe acute respiratory syndrome: a 15-year follow-up from a prospective cohort study.

Bone Res 2020 14;8. Epub 2020 Feb 14.

1Department of Orthopedics and Trauma, Peking University People's Hospital, Beijing, China.

The most severe sequelae after rehabilitation from SARS are femoral head necrosis and pulmonary fibrosis. We performed a 15-year follow-up on the lung and bone conditions of SARS patients. We evaluated the recovery from lung damage and femoral head necrosis in an observational cohort study of SARS patients using pulmonary CT scans, hip joint MRI examinations, pulmonary function tests and hip joint function questionnaires. Read More

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http://dx.doi.org/10.1038/s41413-020-0084-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7018717PMC
February 2020

Autologous fibroblasts induce fibrosis of the nucleus pulposus to maintain the stability of degenerative intervertebral discs.

Bone Res 2020 13;8. Epub 2020 Feb 13.

Shanghai Key Laboratory of Orthopaedic Implants, Department of Orthopaedic Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, P. R. China.

Lumbar degenerative disc diseases cause low back pain (LBP). The maintenance of the height and stability of the intervertebral disc (IVD) space is an effective treatment for LBP. The following study evaluated the effects of fibroblast injection on intervertebral disc degeneration (IDD) in a preclinical setting. Read More

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http://dx.doi.org/10.1038/s41413-019-0082-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7015945PMC
February 2020

Effects of tetrahedral framework nucleic acid/wogonin complexes on osteoarthritis.

Bone Res 2020 10;8. Epub 2020 Feb 10.

1State Key Laboratory of Oral Disease, National Clinical Research Center for Oral Diseases, West China Hosptial of Stomatology, Sichuan University, Chengdu, 610041 China.

Osteoarthritis, a disorder characterized by articular cartilage deterioration, varying degrees of inflammation, and chondrocyte apoptosis, is the most common chronic joint disease. To slow or reverse its progression, inflammation should be inhibited, and chondrocyte proliferation should be promoted. Tetrahedral framework nucleic acids can be internalized by chondrocytes (even inflammatory chondrocytes) and can enhance their proliferation and migration. Read More

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http://dx.doi.org/10.1038/s41413-019-0077-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7010777PMC
February 2020

IgSF11 regulates osteoclast differentiation through association with the scaffold protein PSD-95.

Bone Res 2020 10;8. Epub 2020 Feb 10.

1Department of Pathology and Laboratory Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104 USA.

Osteoclasts are multinucleated, giant cells derived from myeloid progenitors. While receptor activator of NF-κB ligand (RANKL) stimulation is the primary driver of osteoclast differentiation, additional signaling further contributes to osteoclast maturation. Here, we demonstrate that immunoglobulin superfamily member 11 (IgSF11), whose expression increases during osteoclast differentiation, regulates osteoclast differentiation through interaction with postsynaptic density protein 95 (PSD-95), a scaffold protein with multiple protein interaction domains. Read More

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http://dx.doi.org/10.1038/s41413-019-0080-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7010662PMC
February 2020

Inducible expression of Wnt7b promotes bone formation in aged mice and enhances fracture healing.

Bone Res 2020 3;8. Epub 2020 Feb 3.

2Department of Orthopaedic Surgery, Washington University School of Medicine, St. Louis, MO 63110 USA.

There remain unmet clinical needs for safe and effective bone anabolic therapies to treat aging-related osteoporosis and to improve fracture healing in cases of nonunion or delayed union. Wnt signaling has emerged as a promising target pathway for developing novel bone anabolic drugs. Although neutralizing antibodies against the Wnt antagonist sclerostin have been tested, Wnt ligands themselves have not been fully explored as a potential therapy. Read More

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http://dx.doi.org/10.1038/s41413-019-0081-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6997361PMC
February 2020

L-Plastin deficiency produces increased trabecular bone due to attenuation of sealing ring formation and osteoclast dysfunction.

Bone Res 2020 22;8. Epub 2020 Jan 22.

2Department of Orthopedics, University of Maryland School of Medicine, Baltimore, MD USA.

Bone resorption requires the formation of complex, actin-rich cytoskeletal structures. During the early phase of sealing ring formation by osteoclasts, L-plastin regulates actin-bundling to form the nascent sealing zones (NSZ). Here, we show that L-plastin knockout mice produce osteoclasts that are deficient in the formation of NSZs, are hyporesorptive, and make superficial resorption pits in vitro. Read More

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http://dx.doi.org/10.1038/s41413-019-0079-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6976634PMC
January 2020

Focal adhesion protein Kindlin-2 regulates bone homeostasis in mice.

Bone Res 2020 2;8. Epub 2020 Jan 2.

1Guangdong Provincial Key Laboratory of Cell Microenvironment and Disease Research, Shenzhen Key Laboratory of Cell Microenvironment, and Department of Biology, Southern University of Science and Technology, Shenzhen, 518055 China.

Our recent studies demonstrate that the focal adhesion protein Kindlin-2 is critical for chondrogenesis and early skeletal development. Here, we show that deleting Kindlin-2 from osteoblasts using the 2.3-kb mouse transgene minimally impacts bone mass in mice, but deleting Kindlin-2 using the 10-kb mouse transgene, which targets osteocytes and mature osteoblasts, results in striking osteopenia in mice. Read More

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http://dx.doi.org/10.1038/s41413-019-0073-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6946678PMC
January 2020

Disruption of and in cholesterol metabolism causes defects in bone formation and homeostasis through primary cilium formation.

Bone Res 2020 2;8. Epub 2020 Jan 2.

1Department of Diagnostic & Biomedical Sciences, The University of Texas Health Science Center at Houston, School of Dentistry, Houston, TX USA.

Human linkage studies suggest that craniofacial deformities result from either genetic mutations related to cholesterol metabolism or high-cholesterol maternal diets. However, little is known about the precise roles of intracellular cholesterol metabolism in the development of craniofacial bones, the majority of which are formed through intramembranous ossification. Here, we show that an altered cholesterol metabolic status results in abnormal osteogenesis through dysregulation of primary cilium formation during bone formation. Read More

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http://dx.doi.org/10.1038/s41413-019-0078-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6946666PMC
January 2020

Mesenchymal VEGFA induces aberrant differentiation in heterotopic ossification.

Bone Res 2019 10;7:36. Epub 2019 Dec 10.

1Department of Surgery, University of Michigan, Ann Arbor, MI 48109 USA.

Heterotopic ossification (HO) is a debilitating condition characterized by the pathologic formation of ectopic bone. HO occurs commonly following orthopedic surgeries, burns, and neurologic injuries. While surgical excision may provide palliation, the procedure is often burdened with significant intra-operative blood loss due to a more robust contribution of blood supply to the pathologic bone than to native bone. Read More

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http://dx.doi.org/10.1038/s41413-019-0075-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6904752PMC
December 2019

Metabolic programming determines the lineage-differentiation fate of murine bone marrow stromal progenitor cells.

Bone Res 2019 14;7:35. Epub 2019 Nov 14.

1Department of Molecular Endocrinology, University of Southern Denmark and Odense University Hospital, 5000 Odense, Denmark.

Enhanced bone marrow adipogenesis and impaired osteoblastogenesis have been observed in obesity, suggesting that the metabolic microenvironment regulates bone marrow adipocyte and osteoblast progenitor differentiation fate. To determine the molecular mechanisms, we studied two immortalized murine cell lines of adipocyte or osteoblast progenitors (BMSCs and BMSCs, respectively) under basal and adipogenic culture conditions. At baseline, BMSCs, and BMSCs exhibit a distinct metabolic program evidenced by the presence of specific global gene expression, cellular bioenergetics, and metabolomic signatures that are dependent on insulin signaling and glycolysis in BMSCs versus oxidative phosphorylation in BMSCs. Read More

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http://dx.doi.org/10.1038/s41413-019-0076-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6856123PMC
November 2019

Osteocyte dysfunction promotes osteoarthritis through MMP13-dependent suppression of subchondral bone homeostasis.

Bone Res 2019 5;7:34. Epub 2019 Nov 5.

1Department of Orthopaedic Surgery, University of California, San Francisco, CA 94143 USA.

Osteoarthritis (OA), long considered a primary disorder of articular cartilage, is commonly associated with subchondral bone sclerosis. However, the cellular mechanisms responsible for changes to subchondral bone in OA, and the extent to which these changes are drivers of or a secondary reaction to cartilage degeneration, remain unclear. In knee joints from human patients with end-stage OA, we found evidence of profound defects in osteocyte function. Read More

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http://dx.doi.org/10.1038/s41413-019-0070-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6828661PMC
November 2019

Inhibition of immune checkpoints prevents injury-induced heterotopic ossification.

Bone Res 2019 1;7:33. Epub 2019 Nov 1.

1School of Basic Medical Sciences, Anhui Medical University, 81 Meishan Road, 230032 Hefei, Anhui China.

Heterotopic ossification (HO), true bone formation in soft tissue, is closely associated with abnormal injury/immune responses. We hypothesized that a key underlying mechanism of HO might be injury-induced dysregulation of immune checkpoint proteins (ICs). We found that the earliest stages of HO are characterized by enhanced infiltration of polarized macrophages into sites of minor injuries in an animal model of HO. Read More

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http://dx.doi.org/10.1038/s41413-019-0074-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6823457PMC
November 2019

Human iPSC-derived iMSCs improve bone regeneration in mini-pigs.

Bone Res 2019 24;7:32. Epub 2019 Oct 24.

2Institute for Stem Cell Research and Regenerative Medicine, Medical Faculty, Heinrich Heine University, Düsseldorf, Moorenstr. 5, 40225 Düsseldorf, Germany.

Autologous bone marrow concentrate (BMC) and mesenchymal stem cells (MSCs) have beneficial effects on the healing of bone defects. To address the shortcomings associated with the use of primary MSCs, induced pluripotent stem cell (iPSC)-derived MSCs (iMSCs) have been proposed as an alternative. The aim of this study was to investigate the bone regeneration potential of human iMSCs combined with calcium phosphate granules (CPG) in critical-size defects in the proximal tibias of mini-pigs in the early phase of bone healing compared to that of a previously reported autograft treatment and treatment with a composite made of either a combination of autologous BMC and CPG or CPG alone. Read More

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http://dx.doi.org/10.1038/s41413-019-0069-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6813363PMC
October 2019

S100A4 released from highly bone-metastatic breast cancer cells plays a critical role in osteolysis.

Bone Res 2019 23;7:30. Epub 2019 Sep 23.

1Department of Cell and Developmental Biology, BK21 Program and DRI, Seoul National University, Seoul, Korea.

Bone destruction induced by breast cancer metastasis causes severe complications, including death, in breast cancer patients. Communication between cancer cells and skeletal cells in metastatic bone microenvironments is a principal element that drives tumor progression and osteolysis. Tumor-derived factors play fundamental roles in this form of communication. Read More

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http://dx.doi.org/10.1038/s41413-019-0068-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6804941PMC
September 2019

Inhibition of cyclooxygenase-2 activity in subchondral bone modifies a subtype of osteoarthritis.

Bone Res 2019 11;7:29. Epub 2019 Sep 11.

1Department of Orthopaedic Surgery, The Johns Hopkins University School of Medicine, Baltimore, MD 21205 USA.

Osteoarthritis (OA) causes the destruction of joints. Its pathogenesis is still under investigation, and there is no effective disease-modifying therapy. Here, we report that elevated cyclooxygenase-2 (COX-2) expression in the osteocytes of subchondral bone causes both spontaneous OA and rheumatoid arthritis (RA). Read More

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http://dx.doi.org/10.1038/s41413-019-0071-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6804921PMC
September 2019

Autophagy in bone homeostasis and the onset of osteoporosis.

Bone Res 2019 3;7:28. Epub 2019 Oct 3.

State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, 610041 China.

Autophagy is an evolutionarily conserved intracellular process, in which domestic cellular components are selectively digested for the recycling of nutrients and energy. This process is indispensable for cell homeostasis maintenance and stress responses. Both genetic and functional studies have demonstrated that multiple proteins involved in autophagic activities are critical to the survival, differentiation, and functioning of bone cells, including osteoblasts, osteocytes, and osteoclasts. Read More

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http://dx.doi.org/10.1038/s41413-019-0058-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6804951PMC
October 2019

Ankylosing spondylitis: etiology, pathogenesis, and treatments.

Bone Res 2019 5;7:22. Epub 2019 Aug 5.

1Department of Orthopedics, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, 100730 Beijing, China.

Ankylosing spondylitis (AS), a common type of spondyloarthropathy, is a chronic inflammatory autoimmune disease that mainly affects spine joints, causing severe, chronic pain; additionally, in more advanced cases, it can cause spine fusion. Significant progress in its pathophysiology and treatment has been achieved in the last decade. Immune cells and innate cytokines have been suggested to be crucial in the pathogenesis of AS, especially human leukocyte antigen (HLA)‑B27 and the interleukin‑23/17 axis. Read More

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http://dx.doi.org/10.1038/s41413-019-0057-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6804882PMC

Erythropoietin modulates bone marrow stromal cell differentiation.

Bone Res 2019 25;7:21. Epub 2019 Jul 25.

1Molecular Medicine Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892 USA.

Erythropoietin is essential for bone marrow erythropoiesis and erythropoietin receptor on non-erythroid cells including bone marrow stromal cells suggests systemic effects of erythropoietin. Tg6 mice with chronic erythropoietin overexpression have a high hematocrit, reduced trabecular and cortical bone and bone marrow adipocytes, and decreased bone morphogenic protein 2 driven ectopic bone and adipocyte formation. Erythropoietin treatment (1 200 IU·kg) for 10 days similarly exhibit increased hematocrit, reduced bone and bone marrow adipocytes without increased osteoclasts, and reduced bone morphogenic protein signaling in the bone marrow. Read More

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http://dx.doi.org/10.1038/s41413-019-0060-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6804931PMC

Humanized bone facilitates prostate cancer metastasis and recapitulates therapeutic effects of zoledronic acid in vivo.

Bone Res 2019 21;7:31. Epub 2019 Oct 21.

1Centre in Regenerative Medicine, Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Australia.

Advanced prostate cancer (PCa) is known for its high prevalence to metastasize to bone, at which point it is considered incurable. Despite significant effort, there is no animal model capable of recapitulating the complexity of PCa bone metastasis. The humanized mouse model for PCa bone metastasis used in this study aims to provide a platform for the assessment of new drugs by recapitulating the human-human cell interactions relevant for disease development and progression. Read More

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http://dx.doi.org/10.1038/s41413-019-0072-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6804745PMC
October 2019

Iguratimod: a valuable remedy from the Asia Pacific region for ameliorating autoimmune diseases and protecting bone physiology.

Bone Res 2019 3;7:27. Epub 2019 Sep 3.

1Department of Rheumatology, Qilu Hospital of Shandong University, Ji'nan, 250012 Shandong China.

Autoimmune diseases are affected by complex pathophysiology involving several cell types, cytokines, antibodies, and mimicking factors. Different drugs are used to ameliorate these autoimmune reactions, including nonsteroidal anti-inflammatory drugs (NSAIDs), corticosteroids, antiantibodies, and small molecular drugs (DMARDs), and they are clinically in vogue for diseases such as rheumatoid arthritis (RA). Nevertheless, low cost-effectiveness, reduced efficacy, adverse effects, and patient nonresponse are unappealing factors driving the development of new drugs such as iguratimod. Read More

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http://dx.doi.org/10.1038/s41413-019-0067-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6804744PMC
September 2019

Correction to: Activation of mTORC1 in subchondral bone preosteoblasts promotes osteoarthritis by stimulating bone sclerosis and secretion of CXCL12.

Bone Res 2019;7:26. Epub 2019 Aug 28.

1Department of Orthopedics, Academy of Orthopedics-Guangdong Province, The Third Affiliated Hospital of Southern Medical University, 510630 Guangzhou, China.

[This corrects the article DOI: 10.1038/s41413-018-0041-8.]. Read More

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http://dx.doi.org/10.1038/s41413-019-0065-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6804799PMC

Bench-to-bedside strategies for osteoporotic fracture: From osteoimmunology to mechanosensation.

Bone Res 2019 15;7:25. Epub 2019 Aug 15.

1Department of Orthopedics, Chinese PLA General Hospital, Beijing, China.

Osteoporosis is characterized by a decrease in bone mass and strength, rendering people prone to osteoporotic fractures caused by low-energy forces. The primary treatment strategy for osteoporotic fractures is surgery; however, the compromised and comminuted bones in osteoporotic fracture sites are not conducive to optimum reduction and rigid fixation. In addition, these patients always exhibit accompanying aging-related disorders, including high inflammatory status, decreased mechanical loading and abnormal skeletal metabolism, which are disadvantages for fracture healing around sites that have undergone orthopedic procedures. Read More

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http://dx.doi.org/10.1038/s41413-019-0066-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6804735PMC
August 2019
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Conditional disruption of the gene in chondrocytes during early postnatal growth impairs secondary ossification in the mouse tibial epiphysis.

Bone Res 2019 5;7:24. Epub 2019 Aug 5.

1Musculoskeletal Disease Center, VA Loma Linda Healthcare System, Loma Linda, CA 92357 USA.

In our previous studies, we have found that the prepubertal increase in thyroid hormone levels induces osterix (Osx) signaling in hypertrophic chondrocytes to transdifferentiate them into osteoblasts. To test if expressed in chondrocytes directly contributes to transdifferentiation and secondary ossification, we generated ; mice and knocked out with a single injection of tamoxifen at postnatal day (P) 3 prior to evaluation of the epiphyseal bone phenotype by µCT, histology, and immunohistochemistry (IHC) at P21. Vehicle (oil)-treated ; and tamoxifen-treated, -negative mice were used as controls. Read More

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http://dx.doi.org/10.1038/s41413-019-0064-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6804621PMC

Sustained Akt signaling in articular chondrocytes causes osteoarthritis via oxidative stress-induced senescence in mice.

Bone Res 2019 5;7:23. Epub 2019 Aug 5.

State Key Laboratory of Proteomics, Beijing Proteome Research Center, National Center for Protein Sciences (Beijing), Beijing Institute of Lifeomics, Beijing, 102206 China.

Osteoarthritis (OA) is an age-related disorder that is strongly associated with chondrocyte senescence. The causal link between disruptive PTEN/Akt signaling and chondrocyte senescence and the underlying mechanism are unclear. In this study, we found activated Akt signaling in human OA cartilage as well as in a mouse OA model with surgical destabilization of the medial meniscus. Read More

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http://dx.doi.org/10.1038/s41413-019-0062-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6804644PMC

Evolving concepts in bone infection: redefining "biofilm", "acute vs. chronic osteomyelitis", "the immune proteome" and "local antibiotic therapy".

Bone Res 2019 15;7:20. Epub 2019 Jul 15.

1Center for Musculoskeletal Research, University of Rochester Medical Center, Rochester, NY USA.

Osteomyelitis is a devastating disease caused by microbial infection of bone. While the frequency of infection following elective orthopedic surgery is low, rates of reinfection are disturbingly high. is responsible for the majority of chronic osteomyelitis cases and is often considered to be incurable due to bacterial persistence deep within bone. Read More

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http://dx.doi.org/10.1038/s41413-019-0061-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6804538PMC
July 2019
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The role of GPCRs in bone diseases and dysfunctions.

Bone Res 2019 8;7:19. Epub 2019 Jul 8.

4East China Normal University and Shanghai Changzheng Hospital Joint Research Center for Orthopedic Oncology, Department of Orthopedic Oncology, Shanghai Changzheng Hospital, Second Military Medical University, Shanghai, China.

The superfamily of G protein-coupled receptors (GPCRs) contains immense structural and functional diversity and mediates a myriad of biological processes upon activation by various extracellular signals. Critical roles of GPCRs have been established in bone development, remodeling, and disease. Multiple human GPCR mutations impair bone development or metabolism, resulting in osteopathologies. Read More

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http://dx.doi.org/10.1038/s41413-019-0059-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6804689PMC

Extracellular vesicles from human urine-derived stem cells prevent osteoporosis by transferring CTHRC1 and OPG.

Bone Res 2019 26;7:18. Epub 2019 Jun 26.

1Department of Orthopedics, Xiangya Hospital, Central South University, Changsha, Hunan 410008 China.

Osteoporosis is a debilitating bone disease affecting millions of people. Here, we used human urine-derived stem cells (USCs), which were noninvasively harvested from unlimited and easily available urine, as a "factory" to obtain extracellular vesicles (USC-EVs) and demonstrated that the systemic injection of USC-EVs effectively alleviates bone loss and maintains bone strength in osteoporotic mice by enhancing osteoblastic bone formation and suppressing osteoclastic bone resorption. More importantly, the anti-osteoporotic properties of USC-EVs are not notably disrupted by the age, gender, or health condition (with or without osteoporosis) of the USC donor. Read More

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http://dx.doi.org/10.1038/s41413-019-0056-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6594995PMC
June 2019
10 Reads

Extra-skeletal manifestations in mice affected by -dependent autosomal dominant osteopetrosis type 2 clinical and therapeutic implications.

Bone Res 2019 11;7:17. Epub 2019 Jun 11.

1Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, L'Aquila, Italy.

Autosomal dominant osteopetrosis type 2 (ADO2) is a high-density brittle bone disease characterized by bone pain, multiple fractures and skeletal-related events, including nerve compression syndrome and hematological failure. We demonstrated that in mice carrying the heterozygous mutation, whose human mutant homolog affects patients, the clinical impacts of ADO2 extend beyond the skeleton, affecting several other organs. The hallmark of the extra-skeletal alterations is a consistent perivascular fibrosis, associated with high numbers of macrophages and lymphoid infiltrates. Read More

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http://dx.doi.org/10.1038/s41413-019-0055-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6559989PMC
June 2019
11 Reads

Correction to: Suppressive effects of plumbagin on invasion and migration of breast cancer cells via the inhibition of STAT3 signaling and down-regulation of inflammatory cytokine expressions.

Bone Res 2019 22;7:16. Epub 2019 May 22.

1Shanghai Key Laboratory of Orthopaedic Implants, Department of Orthopaedic Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011 China.

[This corrects the article DOI: 10.4248/BR201304007.]. Read More

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http://dx.doi.org/10.1038/s41413-019-0052-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6531459PMC
May 2019
4 Reads

50 years of scanning electron microscopy of bone-a comprehensive overview of the important discoveries made and insights gained into bone material properties in health, disease, and taphonomy.

Bone Res 2019 22;7:15. Epub 2019 May 22.

Department of Biomaterials, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.

Bone is an architecturally complex system that constantly undergoes structural and functional optimisation through renewal and repair. The scanning electron microscope (SEM) is among the most frequently used instruments for examining bone. It offers the key advantage of very high spatial resolution coupled with a large depth of field and wide field of view. Read More

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http://www.nature.com/articles/s41413-019-0053-z
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http://dx.doi.org/10.1038/s41413-019-0053-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6531483PMC
May 2019
16 Reads

Controlling hypoxia-inducible factor-2α is critical for maintaining bone homeostasis in mice.

Bone Res 2019 13;7:14. Epub 2019 May 13.

1Department of Pharmacology and Dental Therapeutics, School of Dentistry, Chonnam National University, Gwangju, 61186 Korea.

Pathological bone loss is caused by an imbalance between bone formation and resorption. The bone microenvironments are hypoxic, and hypoxia-inducible factor (HIF) is known to play notable roles in bone remodeling. However, the relevant functions of HIF-2α are not well understood. Read More

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http://www.nature.com/articles/s41413-019-0054-y
Publisher Site
http://dx.doi.org/10.1038/s41413-019-0054-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6513851PMC
May 2019
6 Reads

Engineering osteoblastic metastases to delineate the adaptive response of androgen-deprived prostate cancer in the bone metastatic microenvironment.

Bone Res 2019 25;7:13. Epub 2019 Apr 25.

1School of Biomedical Sciences, Faculty of Health and Australian Prostate Cancer Research Centre (APCRC-Q), Institute of Health and Biomedical Innovation (IHBI), Queensland University of Technology (QUT), Brisbane, QLD 4000 Australia.

While stromal interactions are essential in cancer adaptation to hormonal therapies, the effects of bone stroma and androgen deprivation on cancer progression in bone are poorly understood. Here, we tissue-engineered and validated an in vitro microtissue model of osteoblastic bone metastases, and used it to study the effects of androgen deprivation in this microenvironment. The model was established by culturing primary human osteoprogenitor cells on melt electrowritten polymer scaffolds, leading to a mineralized osteoblast-derived microtissue containing, in a 3D setting, viable osteoblastic cells, osteocytic cells, and appropriate expression of osteoblast/osteocyte-derived mRNA and proteins, and mineral content. Read More

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http://dx.doi.org/10.1038/s41413-019-0049-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6486620PMC
April 2019
1 Read

DMP1 prevents osteocyte alterations, FGF23 elevation and left ventricular hypertrophy in mice with chronic kidney disease.

Bone Res 2019 25;7:12. Epub 2019 Apr 25.

1Division of Nephrology and Hypertension, Center for Translational Metabolism and Health, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611 USA.

During chronic kidney disease (CKD), alterations in bone and mineral metabolism include increased production of the hormone fibroblast growth factor 23 (FGF23) that may contribute to cardiovascular mortality. The osteocyte protein dentin matrix protein 1 (DMP1) reduces FGF23 and enhances bone mineralization, but its effects in CKD are unknown. We tested the hypothesis that DMP1 supplementation in CKD would improve bone health, prevent FGF23 elevations and minimize consequent adverse cardiovascular outcomes. Read More

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http://dx.doi.org/10.1038/s41413-019-0051-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6483996PMC
April 2019
8 Reads