Department of Cell & Systems Biology, University of Toronto Scarborough, Toronto, ON M1C 1A4, Canada.
Department of Biological Sciences, University of Toronto Scarborough, Toronto, ON M1C 1A4, Canada.
Int J Mol Sci. 2024 Jun 1;25(11):6134. doi: 10.3390/ijms25116134.
Estrogen (17β-estradiol) deficiency post-menopause alters bone homeostasis whereby bone resorption by osteoclasts exceeds bone formation by osteoblasts, leading to osteoporosis in females. We established an in vitro model to examine the consequences of estrogen withdrawal (E2-WD) on osteoclasts derived from the mouse macrophage RAW 264.7 cell line and utilized it to investigate the mechanism behind the enhanced osteoclast activity post-menopause. We found that a greater population of osteoclasts that underwent E2-WD contained a podosome belt necessary for osteoclasts to adhere and resorb bone and possessed elevated resorptive activity compared to osteoclasts exposed to estrogen (E2) continuously. Our results show that compared to osteoclasts that received E2 continuously, those that underwent E2-WD had a faster rate of microtubule (MT) growth, reduced RhoA activation, and shorter podosome lifespan. Thus, altered podosome and MT dynamics induced by the withdrawal of estrogen supports podosome belt assembly/stability in osteoclasts, which may explain their enhanced bone resorption activity.
绝经后雌激素（17β-雌二醇）缺乏会改变骨稳态，使破骨细胞的骨吸收超过成骨细胞的骨形成，导致女性骨质疏松。我们建立了体外模型来研究雌激素耗竭（E2-WD）对源自鼠巨噬细胞 RAW 264.7 细胞系的破骨细胞的影响，并利用该模型研究绝经后破骨细胞活性增强的机制。我们发现，经历 E2-WD 的破骨细胞群体中，存在着破骨细胞附着和吸收骨所必需的足突带，其吸收活性高于持续暴露于雌激素（E2）的破骨细胞。我们的结果表明，与持续接受 E2 的破骨细胞相比，经历 E2-WD 的破骨细胞具有更快的微管（MT）生长速度、降低的 RhoA 激活和更短的足突寿命。因此，雌激素耗竭诱导的足突和 MT 动力学改变支持破骨细胞中足突带的组装/稳定性，这可能解释了它们增强的骨吸收活性。
