Department of Orthopaedics, Division of Orthopaedics and Traumatology, Nanfang Hospital, Southern Medical University, Guangzhou, China.
Division of Orthopaedics and Traumatology, Guangdong Provincial Key Laboratory of Bone and Cartilage Regeneration Medicine, Nanfang Hospital, Southern Medical University, Guangzhou, China.
J Cell Physiol. 2024 Aug;239(8):e31291. doi: 10.1002/jcp.31291. Epub 2024 May 9.
The intricate orchestration of osteoporosis (OP) pathogenesis remains elusive. Mounting evidence suggests that angiogenesis-driven osteogenesis serves as a crucial foundation for maintaining bone homeostasis. This study aimed to explore the potential of the endothelial platelet-derived growth factor receptor-β (PDGFR-β) in mitigating bone loss through its facilitation of H-type vessel formation. Our findings demonstrate that the expression level of endothelial PDGFR-β is reduced in samples obtained from individuals suffering from OP, as well as in ovariectomy mice. Depletion of PDGFR-β in endothelial cells ameliorates angiogenesis-mediated bone formation in mice. The regulatory influence of endothelial PDGFR-β on H-type vessels is mediated through the PDGFRβ-P21-activated kinase 1-Notch1 intracellular domain signaling cascade. In particular, the endothelium-specific enhancement of PDGFR-β facilitates H-type vessels and their associated bone formation in OP. Hence, the strategic targeting of endothelial PDGFR-β emerges as a promising therapeutic approach for the management of OP in the near future.
骨质疏松症（OP）发病机制的错综复杂仍然难以捉摸。越来越多的证据表明，血管生成驱动的成骨作用是维持骨稳态的关键基础。本研究旨在探讨内皮血小板衍生生长因子受体-β（PDGFR-β）通过促进 H 型血管形成来减轻骨质流失的潜力。我们的研究结果表明，OP 患者和卵巢切除小鼠的样本中内皮 PDGFR-β 的表达水平降低。内皮细胞中 PDGFR-β 的耗竭可改善小鼠的血管生成介导的骨形成。内皮 PDGFR-β 对 H 型血管的调节作用是通过 PDGFRβ-P21 激活激酶 1-Notch1 细胞内结构域信号级联介导的。特别是，内皮细胞特异性增强 PDGFR-β 可促进 OP 中的 H 型血管及其相关的骨形成。因此，内皮 PDGFR-β 的靶向治疗策略有望成为未来治疗 OP 的一种有前途的方法。
