Absence of Cx43 selectively from osteocytes enhances responsiveness to mechanical force in mice

作者：Bivi Nicoletta; Pacheco Costa Rafael; Brun Lucas R; Murphy Thomas R; Farlow Nathan R; Robling Alexander G; Bellido Teresita; Plotkin Lilian I^*

来源：Journal of Orthopaedic Research, 2013, 31(7): 1075-1081.

DOI：10.1002/jor.22341

• connexin43
• bone formation
• mechanical loading
• osteocyte
• beta-catenin

The osteocyte network is crucial for the response of bone to mechanical force. Within this network, connexin43 (Cx43) is thought to mediate the communication of osteocytes and osteoblasts among themselves and the exchange of small molecules with the extracellular milieu. Despite recent advances in understanding Cx43 role for the response of bone cells to mechanical stimulation, the contribution of Cx43 specifically in osteocytes to mechanotransduction in vivo is not well-known. We examined the anabolic response to ulnar axial loading of mice lacking Cx43 in osteocytes (Cx43Ot). Loading induced a greater increase in periosteal bone formation rate in Cx43Ot mice compared to control littermates, resulting from higher mineralizing surface and enhanced mineral apposition rate. Expression of -catenin protein, a molecule implicated in mechanotransduction, was higher in bones from Cx43Ot mice, compared to littermate controls. In addition, MLO-Y4 osteocytic cells knocked-down for Cx43 exhibited higher -catenin protein expression and enhanced response to mechanical stimulation. These findings suggest that osteocytes lacking Cx43 are primed to respond to mechanical stimulation and that absence of Cx43 in osteocytes unleashes bone formation, by a mechanism that might involve accumulation of -catenin.

• 出版日期2013-7