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

BIVI N; PACHECO COSTA R ; BRUN LR; MURPHY T; FARLOW N; ROBLING AG; BELLIDO T; PLOTKIN LI

JOURNAL OF ORTHOPAEDIC RESEARCH

JOHN WILEY & SONS INC

Lugar: New York; Año: 2013 vol. 31 p. 1075 - 1081

0736-0266

The osteocyte network is crucial for the response of bone to mechanical force. Within this net-work, 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 Cx43∆Ot mice compared to control littermates, resulting from higher mineralizing surface and enhanced mineral apposition rate. Expression of β-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 β-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 β-catenin.