ROCK-II inhibition suppresses impaired mechanobiological responses in early estrogen deficient osteoblasts.

Mechanobiological responses by osteoblasts are governed by downstream Rho-ROCK signalling through actin cytoskeleton re-arrangements but whether these responses are influenced by estrogen deficiency during osteoporosis remains unknown. The objective of this study was to determine alterations in the mechanobiological responses of estrogen-deficient osteoblasts and investigate whether an inhibitor of the Rho-ROCK signalling can revert these changes. MC3T3-E1 cells were pre-treated with 10 nM 17-β estradiol for 7 days and further cultured with or without estradiol for next 2 days.

Alterations in osteocyte mediated osteoclastogenesis during estrogen deficiency and under ROCK-II inhibition: An in vitro study using a novel postmenopausal multicellular niche model.

This study sought to derive an enhanced understanding of the complex intracellular interactions that drive bone loss in postmenopausal osteoporosis. We applied an in-vitro multicellular niche to recapitulate cell-cell signalling between osteocytes, osteoblasts and osteoclasts to investigate (1) how estrogen-deficient and mechanically loaded osteocytes regulate osteoclastogenesis and (2) whether ROCK-II inhibition affects these mechanobiological responses. We report that mechanically stimulated and estrogen-deficient osteocytes upregulated RANKL/OPG and M-CSF gene expression, when compared to those treated with 10 nM estradiol.