Osteocytes: The master cells in bone remodelling

Prideaux, Matthew; Findlay, David M.; Atkins, Gerald J.

doi:10.1016/j.coph.2016.02.003

Cited by 174 publications

(154 citation statements)

References 54 publications

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“…These include among others, Dentin matrix protein-1 ( Dmp1 ) and E11/gp38 (a.k.a. podoplanin), which are expressed in the early osteocyte, and sclerostin (encoded by the Sost gene), which is expressed in mature osteocytes (reviewed in [12, 13]). The most widely used Cre transgenic lines for conditional in vivo gene deletion in osteocytes have used various versions of the Dmp1 promoter to drive Cre recombinase expression.…”

Section: Cre Transgenic Mice Used For Studies In Osteocytesmentioning

confidence: 99%

Mouse Cre Models for the Study of Bone Diseases

Dallas

Xie

Shiflett

et al. 2018

Curr Osteoporos Rep

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Recent studies have shown that many bone cell-targeted Cre models are not as specific as originally thought. To ensure accurate data interpretation, it is important for investigators to test for unexpected recombination events due to transient expression of Cre recombinase during development or in precursor cells and to be aware of the potential for germ line recombination of targeted genes as well as the potential for unexpected phenotypes due to the Cre transgene. Although many of the bone-targeted Cre-deleter strains are imperfect and each model has its own limitations, their careful use will continue to provide key advances in our understanding of bone cell function in health and disease.

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Section: Cre Transgenic Mice Used For Studies In Osteocytesmentioning

confidence: 99%

Mouse Cre Models for the Study of Bone Diseases

Dallas

Xie

Shiflett

et al. 2018

Curr Osteoporos Rep

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“…(7,8) As terminally differentiated osteoblasts, osteocytes reside within lacunae in the mineralized bone matrix and extend dendritic processes through an interconnected network of micro-channels called canaliculi that permeate the bone matrix. (7,8) As terminally differentiated osteoblasts, osteocytes reside within lacunae in the mineralized bone matrix and extend dendritic processes through an interconnected network of micro-channels called canaliculi that permeate the bone matrix.…”

Section: Introductionmentioning

confidence: 99%

YAP and TAZ Mediate Osteocyte Perilacunar/Canalicular Remodeling

Kegelman

Coulombe

Jordan

et al. 2019

Journal of Bone and Mineral Research

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Bone fragility fractures are caused by low bone mass or impaired bone quality. Osteoblast/osteoclast coordination determines bone mass, but the factors that control bone quality are poorly understood. Osteocytes regulate osteoblast and osteoclast activity on bone surfaces but can also directly reorganize the bone matrix to improve bone quality through perilacunar/canalicular remodeling; however, the molecular mechanisms remain unclear. We previously found that deleting the transcriptional regulators Yes-associated protein (YAP) and transcriptional co-activator with PDZ-motif (TAZ) from osteoblast-lineage cells caused lethality in mice due to skeletal fragility. Here, we tested the hypothesis that YAP and TAZ regulate osteocyte-mediated bone remodeling by conditional ablation of both YAP and TAZ from mouse osteocytes using 8 kb-DMP1-Cre. Osteocyte-conditional YAP/TAZ deletion reduced bone mass and dysregulated matrix collagen content and organization, which together decreased bone mechanical properties. Further, YAP/TAZ deletion impaired osteocyte perilacunar/canalicular remodeling by reducing canalicular network density, length, and branching, as well as perilacunar flourochrome-labeled mineral deposition. Consistent with recent studies identifying TGF-β as a key inducer of osteocyte expression of matrix-remodeling enzymes, YAP/TAZ deletion in vivo decreased osteocyte expression of matrix proteases MMP13, MMP14, and CTSK. In vitro, pharmacologic inhibition of YAP/TAZ transcriptional activity in osteocyte-like cells abrogated TGF-β-induced matrix protease gene expression. Together, these data show that YAP and TAZ control bone matrix accrual, organization, and mechanical properties by regulating osteocyte-mediated bone remodeling. Elucidating the signaling pathways that control perilacunar/canalicular remodeling may enable future therapeutic targeting of bone quality to reverse skeletal fragility.

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“…*Significant difference from the negative control (NC) group with p < 0.05; **significant difference from the NC group with p < 0.01. DAPI: 4′,6-diamidino-2-phenylindole; GFP: green fluorescent protein; siRNA: small interfering RNA [Color figure can be viewed at wileyonlinelibrary.com] 2015;Prideaux, Findlay, & Atkins, 2016). Osteocytes can also play a critical role in transducing some important exogenous anabolic or catabolic hormonal stimuli.…”

mentioning

confidence: 99%

Pulsed electromagnetic fields regulate osteocyte apoptosis, RANKL/OPG expression, and its control of osteoclastogenesis depending on the presence of primary cilia

Wang

Tang

et al. 2018

Journal Cellular Physiology

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Growing evidence has shown that pulsed electromagnetic fields (PEMF) can modulate bone metabolism in vivo and regulate the activities of osteoblasts and osteoclasts in vitro. Osteocytes, accounting for 95% of bone cells, act as the major mechanosensors in bone for transducing external mechanical signals and producing cytokines to regulate osteoblastic and osteoclastic activities. Targeting osteocytic signaling pathways is becoming an emerging therapeutic strategy for bone diseases. We herein systematically investigated the changes of osteocyte behaviors, functions, and its regulation on osteoclastogenesis in response to PEMF. The osteocyte‐like MLO‐Y4 cells were exposed to 15 Hz PEMF stimulation with different intensities (0, 5, and 30 Gauss [G]) for 2 hr. We found that the cell apoptosis and cytoskeleton organization of osteocytes were regulated by PEMF with an intensity‐dependent manner. Moreover, PEMF exposure with 5 G significantly inhibited apoptosis‐related gene expression and also suppressed the gene and protein expression of the receptor activator of nuclear factor κB ligand/osteoprotegerin (RANKL/OPG) ratio in MLO‐Y4 cells. The formation, maturation, and osteoclastic bone‐resorption capability of in vitro osteoclasts were significantly suppressed after treated with the conditioned medium from PEMF‐exposed (5 G) osteocytes. Our results also revealed that the inhibition of osteoclastic formation, maturation, and bone‐resorption capability induced by the conditioned medium from 5 G PEMF‐exposed osteocytes was significantly attenuated after abrogating primary cilia in osteocytes using the polaris siRNA transfection. Together, our findings highlight that PEMF with 5 G can inhibit cellular apoptosis, modulate cytoskeletal distribution, and decrease RANKL/OPG expression in osteocytes, and also inhibit osteocyte‐mediated osteoclastogenesis, which requires the existence of primary cilia in osteocytes. This study enriches our basic knowledge for further understanding the biological behaviors of osteocytes and is also helpful for providing a more comprehensive mechanistic understanding of the effect of electromagnetic stimulation on bone and relevant skeletal diseases (e.g., bone fracture and osteoporosis).

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Osteocytes: The master cells in bone remodelling

Cited by 174 publications

References 54 publications

Mouse Cre Models for the Study of Bone Diseases

Mouse Cre Models for the Study of Bone Diseases

YAP and TAZ Mediate Osteocyte Perilacunar/Canalicular Remodeling

Pulsed electromagnetic fields regulate osteocyte apoptosis, RANKL/OPG expression, and its control of osteoclastogenesis depending on the presence of primary cilia

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