However, how the external loading signal in bone is transmitted at the cellular level, especially to and between osteocytes, is not well understood,

and the relationship surrounding mechanical stress, cellular reactions, and bone remodeling is still not fully resolved. This review describes the in vivo and in vitro evidence relating connective tissue growth factor (CTGF or CCN2) to compressive mechanical forces in osteocytes and discussed the molecular Selleckchem PR171 and cellular mechanisms of mechanosensing and mechanotransduction leading to the induction of osteocyte apoptosis and, thereafter, to an increase in bone resorption. Osteocytes are the most numerous cellular component in bone tissue, and are embedded in the calcified bone matrix, where they communicate with each other and with osteoblasts on the bone surface through slender processes comprising gap junctions [31]. Time-lapse

imaging of calvarial explant cultures using transgenic Fasudil supplier mice with green fluorescent protein (GFP)-targeted to osteocytes [32] has been used to observe living osteocytes within their lacunae [33]. Unexpectedly, far from being an inactive, quiescent cell type, the osteocyte was found to be highly dynamic. In a model of experimental tooth movement, when a force is loaded to a tooth, there is selective induction of bone resorption by osteoclasts on the pressured side in the alveolar bone and bone formation by osteoblasts on the tensioned side [34]. This differential stress causes the tooth to move in a specified direction. Using this experimental tooth movement model, we have previously demonstrated that osteocytes respond early to mechanical stress and produce osteopontin

(OPN) in its action as a mechanotransducer, suggesting that osteocytes Tau-protein kinase play a critical role in bone resorption triggered by mechanical force [28]. Furthermore, Tatsumi et al. [29] reported that osteocyte-ablated transgenic mice were resistant to tail suspension-induced bone loss. These results indicated that osteocytes are the major mechanosensitive cells in bone tissues, and are involved in regulation of osteoclastic bone resorption and remodeling. Primary cultures of chick osteocytes in vitro [35] and living bone ex vivo [36] show that functional gap junctions are retained between osteocytes and between osteocytes and osteoblasts. the gap junction connects osteocyte each other and connects osteocyte and osteoblast to mediate their intercellular communication. These findings are consistent with the ability of osteocytes to respond to and transmit signals over long distances while embedded apart from each other in a calcified matrix [35] and [36]. Gap junctional intercellular communication (GJIC) is thus thought to play an important role in the integration and synchronization of bone remodeling.