Osteocytic miR21 deficiency improves bone strength independent of sex despite having sex divergent effects on osteocyte viability and bone turnover. (8th October 2019)

• Record Type: Journal Article
• Authors: Davis, Hannah M.; Deosthale, Padmini J.; Pacheco‐Costa, Rafael; Essex, Alyson L.; Atkinson, Emily G.; Aref, Mohammad W.; Dilley, Julian E.; Bellido, Teresita; Ivan, Mircea; Allen, Matthew R.; Plotkin, Lilian I.
• Is Part Of: FEBS journal. Volume 287:Number 5(2020)
• Page Start: 941
• Page End: 963
• Publication Date: 2019-10-08
• Subjects: apoptosis -- bone -- cytokine -- microRNA -- miR21 -- osteocyte -- sexual‐dimorphism; Biochemistry -- Periodicals; Molecular biology -- Periodicals; Pathology, Molecular -- Periodicals; 572
• DOI: 10.1111/febs.15066
• Languages: English
• ISSNs: 1742-464X

Abstract

Abstract : 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. Abstract : The microRNA miR21 regulates bone metabolism by acting directly on osteoblasts, the bone‐forming cells, and osteoclasts, the bone resorbing cells; but the role of miR21 on osteocytes, the bone matrix‐embedded cells that control the actions of osteoblasts and osteoclasts, is not clear. We report herein that osteocytic miR21 exerts sex‐divergent paracrine actions on osteoblasts and osteoclasts, while enhancing bone mechanical properties in a sex‐independent manner.