title: Enhanced periosteal and endocortical responses to axial tibial compression loading in conditional connexin43 deficient mice.
abstract: The gap junction protein, connexin43 (Cx43) is involved in mechanotransduction in bone. Recent studies using in vivo models of conditional Cx43 gene (Gja1) deletion in the osteogenic linage have generated inconsistent results, with Gja1 ablation resulting in either attenuated or enhanced response to mechanical load, depending upon the skeletal site examined or the type of load applied. To gain further insights on Cx43 and mechanotransduction, we examined bone formation response at both endocortical and periosteal surfaces in 2-month-old mice with conditional Gja1 ablation driven by the Dermo1 promoter (cKO). Relative to wild type (WT) littermates, it requires a larger amount of compressive force to generate the same periosteal strain in cKO mice. Importantly, cKO mice activate periosteal bone formation at a lower strain level than do WT mice, suggesting an increased sensitivity to mechanical load in Cx43 deficiency. Consistently, trabecular bone mass also increases in mutant mice upon load, while it decreases in WT. On the other hand, bone formation actually decreases on the endocortical surface in WT mice upon application of axial mechanical load, and this response is also accentuated in cKO mice. These changes are associated with increase of Cox-2 in both genotypes and further decrease of Sost mRNA in cKO relative to WT bones. Thus, the response of bone forming cells to mechanical load differs between trabecular and cortical components, and remarkably between endocortical and periosteal envelopes. Cx43 deficiency enhances both the periosteal and endocortical response to mechanical load applied as axial compression in growing mice.
authors.affiliation: Division of Bone and Mineral Diseases, Department of Internal Medicine, Washington University in St Louis, St Louis, Missouri, United States of America. Sgrimsto@dom.wustl.edu
authors.forename: Susan K
authors.initials: SK
authors.lastname: Grimston
authors.forename: Marcus P
authors.initials: MP
authors.lastname: Watkins
authors.forename: Michael D
authors.initials: MD
authors.lastname: Brodt
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Silva
authors.forename: Roberto
authors.initials: R
authors.lastname: Civitelli
mesh_terms: D000818:Animals; D001696:Biomechanical Phenomena / Q000235:genetics; D019245:Compressive Strength / Q000502:physiology*; D018031:Connexin 43 / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010012:Osteogenesis / Q000235:genetics; D010521:Periosteum / Q000502:physiology*; D013977:Tibia / Q000502:physiology*; D016474:Weight-Bearing / Q000502:physiology
chemical_list: D018031:Connexin 43