Erythropoietin regulates osteoclast formation via up-regulating PPARγ expression

文献类型： 外文期刊

第一作者： Liu, Xiao

作者： Liu, Xiao;Wu, Yifan;Gao, Xiang;Liu, Liang;Geng, Huan;Zhou, Mengxue;Zhai, Lei

作者机构：

关键词： EPO; Bone remodeling; Trabecular; Osteoblast differentiation; Osteocyte

期刊名称：MOLECULAR MEDICINE （ 影响因子：6.4； 五年影响因子：6.3 ）

ISSN： 1076-1551

年卷期： 2024 年 30 卷 1 期

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收录情况： SCI

摘要： Erythropoietin (EPO), expressed in red blood progenitor cells, primarily regulates erythropoiesis by binding to its receptor. Besides anemia, recent studies have identified new therapeutic indications for EPO that are not connected to red blood cell formation. Elevated EPO levels harm bone homeostasis in adult organisms and are associated with increased osteoclast; however, the underlying molecular mechanisms remain unclear. This study demonstrated that EPO enhanced osteoclast differentiation and bone resorption in vitro. We showed that EPO promoted osteoclast formation by up-regulating PPAR gamma expression through activating the Jak2/ERK signaling pathway. Consistently, PPAR gamma antagonists rescued the hyperactivation of osteoclasts due to EPO, while PPAR gamma agonists reversed the EMP9-mediated decrease in osteoclast differentiation. Further, exposing female mice to EPO for two months led to a decrease in bone mass and increased osteoclast numbers. The present results suggested that EPO promotes osteoclastogenesis by regulating the Jak2/ERK/ PPAR gamma signaling pathway. From a clinical perspective, the risk of compromised bone health should be considered when using EPO to treat anemia in post-operative patients with intertrochanteric fractures of the femur, as it could significantly impact the patient's recovery and quality of life.

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