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

Nicoletta Bivi, Rafael Pacheco-Costa, Lucas R. Brun, Thomas R. Murphy, Nathan R. Farlow, Alexander G. Robling, Teresita Bellido, Lilian I. Plotkin

Research output: Contribution to journalArticle

59 Scopus citations

Abstract

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 (Cx43 ΔOt). Loading induced a greater increase in periosteal bone formation rate in Cx43ΔOt 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 Cx43ΔOt 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.

Original languageEnglish (US)
Pages (from-to)1075-1081
Number of pages7
JournalJournal of Orthopaedic Research
Volume31
Issue number7
DOIs
StatePublished - Jul 1 2013

Keywords

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

ASJC Scopus subject areas

  • Orthopedics and Sports Medicine

Fingerprint Dive into the research topics of 'Absence of Cx43 selectively from osteocytes enhances responsiveness to mechanical force in mice'. Together they form a unique fingerprint.

  • Cite this