Deletion of p16 prevents estrogen deficiency-induced osteoporosis by inhibiting oxidative stress and osteocyte senescence.

Deletion of p16 prevents estrogen deficiency-induced osteoporosis by inhibiting oxidative stress and osteocyte senescence. Am J Transl Res. 2020;12(2):672-683 Authors: Li J, Karim MA, Che H, Geng Q, Miao D Abstract To investigate whether p16 deletion can prevent osteoporosis caused by estrogen deficiency, we first confirmed that p16 protein expression levels were significantly up-regulated in bony tissue of ovariectomized (OVX) wild-type mice. Eight-week-old wild-type and p16-/- mice were then sham-operated or bilateral OVX. After 12 weeks, the bone phenotypes of all models were analyzed by radiography, micro-computed tomography, histology, immunohistochemistry, and molecular biology. The results showed that p16 deficiency could rescue OVX-induced osteoporosis by significantly increased bone mineral density, trabecular bone volume, total collagen positive area, osteoblast number, type I collagen positive area, fibroblast colony-forming unit (CFU-f) and alkaline phosphatase-positive CFU-f with up-regulation of the mRNA expression levels of Alp, Runx2, type I collagen and osteocalcin, and significantly reduced osteoclast surface and the ratio of RANKL/OPG mRNA expression level. Furthermore, we also demonstrated that p16 deletion inhibited OVX-induced oxidative stress and bone cell senescence, such as a significant decrease in reactive oxygen species levels, up-regulation of superoxide dismutase 1 and 2 protein expression levels, and re...
Source: American Journal of Translational Research - Category: Research Tags: Am J Transl Res Source Type: research