Connexin43 deficiency reduces the sensitivity of cortical bone to the effects of muscle paralysis

Susan K. Grimston, Daniel B. Goldberg, Marcus Watkins, Michael D. Brodt, Matthew J. Silva, Roberto Civitelli

Research output: Contribution to journalArticle

54 Scopus citations

Abstract

We have shown previously that the effect of mechanical loading on bone depends in part on connexin43 (Cx43). To determine whether Cx43 is also involved in the effect of mechanical unloading, we have used botulinum toxin A (BtxA) to induce reversible muscle paralysis in mice with a conditional deletion of the Cx43 gene in osteoblasts and osteocytes (cKO). BtxA injection in hind limb muscles of wild-type (WT) mice resulted in significant muscle atrophy and rapid loss of trabecular bone. Bone loss reached a nadir of about 40% at 3 weeks after injection, followed by a slow recovery. A similar degree of trabecular bone loss was observed in cKO mice. By contrast, BtxA injection in WT mice significantly increased marrow area and endocortical osteoclast number and decreased cortical thickness and bone strength. These changes did not occur in cKO mice, whose marrow area is larger, osteoclast number higher, and cortical thickness and bone strength lower relative to WT mice in basal conditions. Changes in cortical structure occurring in WT mice had not recovered 19 weeks after BtxA injection despite correction of the early osteoclast activation and a modest increase in periosteal bone formation. Thus BtxA-induced muscle paralysis leads to rapid loss of trabecular bone and to changes in structural and biomechanical properties of cortical bone, neither of which are fully reversed after 19 weeks. Osteoblast/osteocyte Cx43 is involved in the adaptive responses to skeletal unloading selectively in the cortical bone via modulation of osteoclastogenesis on the endocortical surface.

Original languageEnglish
Pages (from-to)2151-2160
Number of pages10
JournalJournal of Bone and Mineral Research
Volume26
Issue number9
DOIs
StatePublished - Sep 1 2011

Keywords

  • BONE MORPHOLOGY
  • CONNEXIN 43
  • MECHANICAL LOAD

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