Lanzolla Giulia, Merceron Christophe, Khan Mohd Parvez, Sabini Elena, Giaccia Amato, Schipani Ernestina
Department of Orthopaedic Surgery, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA 19104, United States.
Department of Orthopaedic Surgery, School of Medicine, University of Michigan, Ann Arbor, MI 48109, United States.
JBMR Plus. 2024 Apr 15;8(6):ziae052. doi: 10.1093/jbmrpl/ziae052. eCollection 2024 Jun.
Erythropoietin (EPO), primarily produced by interstitial fibroblasts in the kidney during adulthood, and its receptor are well-known for their crucial role in regulating erythropoiesis. Recent research has unveiled an additional function of circulating EPO in the control of bone mass accrual and homeostasis through its receptor, which is expressed in both osteoblasts and osteoclasts. Notably, cells of the osteoblast lineage can produce and secrete functional EPO upon activation of the hypoxia signaling pathway. However, the physiological relevance of osteoblastic EPO remains to be fully elucidated. This study aimed to investigate the potential role of osteoblastic EPO in regulating bone mass accrual and erythropoiesis in young adult mice. To accomplish this, we employed a mutant mouse model lacking EPO specifically in mesenchymal progenitors and their descendants. Our findings indicate that in vivo loss of EPO in the osteoblast lineage does not significantly affect either bone mass accrual or erythropoiesis in young adult mice. Further investigations are necessary to comprehensively understand the potential contribution of EPO produced and secreted by osteoblast cells during aging, repair, and under pathological conditions.
促红细胞生成素（EPO）在成年期主要由肾脏中的间质成纤维细胞产生，其受体因在调节红细胞生成中起关键作用而闻名。最近的研究揭示了循环EPO通过其受体在控制骨量积累和内环境稳定方面的额外功能，该受体在成骨细胞和破骨细胞中均有表达。值得注意的是，成骨细胞谱系的细胞在缺氧信号通路激活后可产生并分泌功能性EPO。然而，成骨细胞EPO的生理相关性仍有待充分阐明。本研究旨在探讨成骨细胞EPO在调节年轻成年小鼠骨量积累和红细胞生成中的潜在作用。为实现这一目标，我们采用了一种在间充质祖细胞及其后代中特异性缺失EPO的突变小鼠模型。我们的研究结果表明，成骨细胞谱系中EPO的体内缺失对年轻成年小鼠的骨量积累或红细胞生成均无显著影响。有必要进行进一步研究，以全面了解成骨细胞在衰老、修复和病理条件下产生和分泌的EPO的潜在作用。
