Department of Anatomy, Cell Biology & Physiology, Indiana University School of Medicine, Indianapolis, IN, USA.
Center for Musculoskeletal Health, Indianapolis, IN, USA.
FEBS J. 2020 Mar;287(5):941-963. doi: 10.1111/febs.15066. Epub 2019 Oct 8.
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.
成骨细胞在介导细胞间通讯和调节骨稳态方面发挥着关键作用，成骨细胞凋亡与骨吸收增加有关。miR21 是一种致癌 microRNA，通过直接作用于成骨细胞和破骨细胞来调节骨代谢，但它在成骨细胞中的作用尚不清楚。在这里，我们表明成骨细胞 miR21 缺失在骨骼中具有性别差异的影响。在女性中，miR21 缺失会降低成骨细胞的活力，但会抑制骨转换。相反，在男性中，miR21 缺失会增加成骨细胞的活力，但会刺激骨转换并增强骨结构。此外，miR21 缺失在两性中成骨细胞细胞因子的产生上表现出不同的作用。有趣的是，尽管有这些变化，但 miR21 缺失在两性中都增加了骨的机械性能，尽管在男性中更为明显。总的来说，我们的研究结果表明，miR21 在成骨细胞中发挥着性别差异和性别等同的作用，通过对成骨细胞和破骨细胞的旁分泌作用，调节成骨细胞的活力，并改变骨代谢，在男性和女性中存在差异，而独立于性别影响骨的机械性能。
