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The aim of this study was to investigate the mechanism of bone remodeling while focusing on the

integrity of osteocyte network. Both an in vitro experimental system that could apply local mechanical

damage to the cultured osteocytes and an animal model that could give a fatigue microcrack to a mouse

tibia were developed. A large deformation of the culture substrate or bone matrix damaged the osteocyte

network, and apoptotic cells were derived around the necrotic osteocytes. This apoptotic cell induction

would be a key response for initiating bone remodeling, by which a damaged bone matrix could be

repaired locally and appositional bone formation would be occurred to compensate the drop of bone

strength.

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