Open Access
Osteocyte-Driven Bone Remodeling
TLDR
Osteocytes, the most abundant cells in bone, have been long postulated to detect and respond to mechanical and hormonal stimuli and to coordinate the function of osteoblasts and osteoclasts as mentioned in this paper.Abstract:
Osteocytes, the most abundant cells in bone, have been long postulated to detect and respond to mechanical and hormonal stimuli and to coordinate the function of osteoblasts and osteoclasts. The discovery that the inhibitor of bone formation sclerostin is primarily expressed in osteocytes in bone and downregulated by anabolic stimuli provided a mechanism by which osteocytes influence the activity of osteoblasts. Advances of the last few years provided experimental evidence demonstrating that osteocytes also participate in the recruitment of osteoclasts and the initiation of bone remodeling. Apoptotic osteocytes trigger yet-to-be-identified signals that attract osteoclast precursors to specific areas of bone, which in turn differentiate to mature, bone-resorbing osteoclasts. Osteocytes are also the source of molecules that regulate the generation and activity of osteoclasts, such as OPG and RANKL; and genetic manipulations of the mouse genome leading to loss or gain of function or to altered expression of either molecule in osteocytes markedly affect bone resorption. This review highlights these investigations and discusses how the novel concept of osteocyte-driven bone resorption and formation impacts our understanding of the mechanisms by which current therapies control bone remodeling.read more
Citations
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Journal ArticleDOI
Biology of Bone Tissue: Structure, Function, and Factors That Influence Bone Cells
Rinaldo Florencio-Silva,Gisela Rodrigues da Silva Sasso,Estela Sasso-Cerri,Manuel Simões,Paulo Sérgio Cerri +4 more
TL;DR: Current data about the structure and functions of bone cells and the factors that influence bone remodeling are discussed, indicating the dynamic nature of bone tissue.
Journal ArticleDOI
Inflammation, fracture and bone repair
Florence Loi,Luis A. Córdova,Luis A. Córdova,Jukka Pajarinen,Tzuhua Lin,Zhenyu Yao,Stuart B. Goodman +6 more
TL;DR: In this review, a comprehensive summary of the literature related to inflammation and bone repair is provided, placing special emphasis on the underlying cellular and molecular mechanisms, and potential interventions that can favorably modulate the outcome of clinical conditions that involve bone repair.
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Oxidative stress in bone remodeling: role of antioxidants.
TL;DR: Nutritional approaches to antioxidant strategies, in animals or selected groups of patients with osteoporosis or inflammatory bone diseases, suggest the antioxidant use in anti-resorptive therapies for the treatment and prevention of bone loss.
Journal ArticleDOI
Role of Thyroid Hormones in Skeletal Development and Bone Maintenance
TL;DR: The skeleton represents an ideal physiological system in which to characterize thyroid hormone transport, metabolism, and action during development and adulthood and in response to injury, and will provide new insights into cell-specific molecular mechanisms and may ultimately identify novel therapeutic targets for chronic degenerative diseases such as osteoporosis and osteoarthritis.
Journal ArticleDOI
Osteocytes mediate the anabolic actions of canonical Wnt/β-catenin signaling in bone
Xiaolin Tu,Jesus Delgado-Calle,Keith W. Condon,Marta Maycas,Huajia Zhang,Nadia Carlesso,Makoto Mark Taketo,David B. Burr,Lilian I. Plotkin,Teresita Bellido,Teresita Bellido +10 more
TL;DR: In this article, the authors show that activation of canonical Wnt signaling exclusively in osteocytes induces bone anabolism and triggers Notch signaling without affecting survival in dascatOt mice.
References
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The Amazing Osteocyte
TL;DR: Osteocytes compose 90% to 95% of all bone cells in adult bone and are the longest lived bone cell, up to decades within their mineralized environment.
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Inhibition of osteoblastogenesis and promotion of apoptosis of osteoblasts and osteocytes by glucocorticoids. Potential mechanisms of their deleterious effects on bone.
TL;DR: Evidence is provided that glucocorticoid-induced bone disease arises from changes in the numbers of bone cells, whereas decreased production and apoptosis of osteoblasts would account for the decline in bone formation and trabecular width.
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Evidence for osteocyte regulation of bone homeostasis through RANKL expression
Tomoki Nakashima,Mikihito Hayashi,Takanobu Fukunaga,Kosaku Kurata,Masatsugu Oh-hora,Jian Q. Feng,Lynda F. Bonewald,Tatsuhiko Kodama,Anton Wutz,Erwin F. Wagner,Josef M. Penninger,Hiroshi Takayanagi,Hiroshi Takayanagi +12 more
TL;DR: It is found that purified osteocytes express a much higher amount of receptor activator of nuclear factor-κB ligand (RANKL) and have a greater capacity to support osteoclastogenesis in vitro than osteoblasts and bone marrow stromal cells.
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MT1-MMP-Deficient Mice Develop Dwarfism, Osteopenia, Arthritis, and Connective Tissue Disease due to Inadequate Collagen Turnover
Kenn Holmbeck,Paolo Bianco,John J. Caterina,Susan Yamada,Mark Kromer,Sergei A. Kuznetsov,Mahesh H. Mankani,Pamela Gehron Robey,A. Robin Poole,Isabelle Pidoux,Jerrold M. Ward,Henning Birkedal-Hansen +11 more
TL;DR: The findings demonstrate the pivotal function of MT1-MMP in connective tissue metabolism, and illustrate that modeling of the soft connective tissues matrix by resident cells is essential for the development and maintenance of the hard tissues of the skeleton.
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Mechanical stimulation of bone in vivo reduces osteocyte expression of Sost/sclerostin
Alexander G. Robling,Alexander G. Robling,Paul J. Niziolek,Lee Ann Baldridge,Keith W. Condon,Matthew R. Allen,Imranul Alam,Sara M. Mantila,Jelica Gluhak-Heinrich,Teresita Bellido,Stephen E. Harris,Charles H. Turner,Charles H. Turner +12 more
TL;DR: Modulation of sclerostin levels appears to be a finely tuned mechanism by which osteocytes coordinate regional and local osteogenesis in response to increased mechanical stimulation, perhaps via releasing the local inhibition of Wnt/Lrp5 signaling.