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Osteocytic miR21 deficiency improves bone strength independent of sex despite having sex divergent effects on osteocyte viability and bone turnover
Author(s) -
Davis Hannah M.,
Deosthale Padmini J.,
PachecoCosta Rafael,
Essex Alyson L.,
Atkinson Emily G.,
Aref Mohammad W.,
Dilley Julian E.,
Bellido Teresita,
Ivan Mircea,
Allen Matthew R.,
Plotkin Lilian I.
Publication year - 2020
Publication title -
the febs journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 204
eISSN - 1742-4658
pISSN - 1742-464X
DOI - 10.1111/febs.15066
Subject(s) - osteocyte , bone remodeling , medicine , endocrinology , biology , paracrine signalling , osteoblast , bone cell , bone resorption , microbiology and biotechnology , receptor , in vitro , biochemistry
Osteocytes play a critical role in mediating cell–cell communication and regulating bone homeostasis, and osteocyte apoptosis is associated with increased bone resorption. miR21, an oncogenic microRNA, regulates bone metabolism by acting directly on osteoblasts and osteoclasts, but its role in osteocytes is not clear. Here, we show that osteocytic miR21 deletion has sex‐divergent effects in bone. In females, miR21 deletion reduces osteocyte viability, but suppresses bone turnover. Conversely, in males, miR21 deletion increases osteocyte viability, but stimulates bone turnover and enhances bone structure. Further, miR21 deletion differentially alters osteocyte cytokine production in the two sexes. Interestingly, despite these changes, miR21 deletion increases bone mechanical properties in both sexes, albeit to a greater extent in males. Collectively, our findings suggest that miR21 exerts both sex‐divergent and sex‐equivalent roles in osteocytes, regulating osteocyte viability and altering bone metabolism through paracrine actions on osteoblasts and osteoclasts differentially in males vs females, whereas, influencing bone mechanical properties independent of sex.