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Osteocyte regulation of bone quality in homeostasis and in skeletal disease


Osteocytes are the most numerous cells in bone, working from within the mineralized matrix to exert control over their local environment and cells on the bone surface. Healthy osteocytes are key to bone homeostasis, but the full functional importance of their local remodeling activity, called perilacunar/canalicular remodeling (PLR), is only recently being discovered. This work uses multiple mouse models to investigate the molecular mechanisms controlling osteocyte PLR and demonstrates that repression of PLR causes severe loss of bone material quality. Additionally, osteocyte dysfunction is shown to disrupt bone homeostasis during skeletal disease and to promote degradation of overlying cartilage in the joint. Finally, we begin to determine the extent to which PLR is mechanosensitive, revealing distinct site- and magnitude-specific modulation of osteocyte behavior with applied load. Together these findings reveal new essential roles for osteocytes and PLR within bone and joints during homeostasis and disease.

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