期刊
JBMR PLUS
卷 2, 期 4, 页码 206-216出版社
WILEY
DOI: 10.1002/jbm4.10035
关键词
AGING; APOPTOSIS; CONNEXIN 43; OSTEOCYTE; GENETIC ANIMAL MODELS
资金
- National Institutes of Health [R01-AR053643]
- NIH [T32-AR065971]
- NIH Research Supplement to Promote Diversity in Health-Related Research [3R01AR067210-03S1]
- Coordination of Improvement of Higher Level Personnel (CAPES), Brazil [232636/2014-1]
- IUPUI, Life-Health Sciences Internship Program
- CTSI summer scholars program at IUPUI
- IUSM SRPinAM: T-35 NIH training grant
Young, skeletally mature mice lacking Cx43 in osteocytes exhibit increased osteocyte apoptosis and decreased bone strength, resembling the phenotype of old mice. Further, the expression of Cx43 in bone decreases with age, suggesting a contribution of reduced Cx43 levels to the age-related changes in the skeleton. We report herein that Cx43 overexpression in osteocytes achieved by using the DMP1-8kb promoter (Cx43OT mice) attenuates the skeletal cortical but not trabecular bone phenotype of aged, 14-monthold mice. The percentage of Cx43-expressing osteocytes was higher in Cx43(OT) mice, whereas the percentage of Cx43-positive osteoblasts remained similar to wild-type (WT) littermate control mice. The percentage of apoptotic osteocytes and osteoblasts was increased in aged WT mice compared with skeletally mature, 6-month-old WT mice, and the percentage of apoptotic osteocytes, but not osteoblasts, was decreased in age-matched Cx43(OT) mice. Aged WT mice exhibited decreased bone formation and increased bone resorption as quantified by histomorphometric analysis and circulating markers compared with skeletally mature mice. Further, aged WT mice exhibited the expected decrease in bone biomechanical structural and material properties compared with young mice. Cx43 overexpression prevented the increase in osteoclasts and decrease in bone formation on the endocortical surfaces and the changes in circulating markers in the aged mice. Moreover, the ability of bone to resist damage was preserved in aged Cx43(OT) mice both at the structural and material level. All together, these findings suggest that increased Cx43 expression in osteocytes ameliorates age-induced cortical bone changes by preserving osteocyte viability and maintaining bone formation, leading to improved bone strength. (C) 2018 American Society for Bone and Mineral Research.
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