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

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.

SUBMITTER: Grimston SK

PROVIDER: S-EPMC3306012 | biostudies-literature | 2011 Sep

REPOSITORIES: biostudies-literature

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

Grimston Susan K SK Goldberg Daniel B DB Watkins Marcus M Brodt Michael D MD Silva Matthew J MJ Civitelli Roberto R

Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 20110901 9

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 ...[more]

PMID: 21590735

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Dataset Information

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

Publications

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

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