Wang Zhengchao, Zhu Pengfei, Li Hongmei, Ye Bo, Luo Qiong, Cheng Jiangxia, Cai Yu
Department of Sports Medicine, Wuhan Fourth Hospital, Wuhan, China.
Hubei Provincial Sports Medicine Center, Wuhan, China.
J Cell Mol Med. 2025 Apr;29(7):e70515. doi: 10.1111/jcmm.70515.
Chronic degenerative changes in cartilage and subchondral bone that lead to instability of the cartilage microenvironment are essential for the development of osteoarthritis (OA) in the old. Synchronous repair of cartilage and subchondral bone may be a key strategy for OA treatment. PDGF-BB effectively promoted chondrocyte regeneration and angiogenesis. However, the mechanisms by which PDGF-BB affects subchondral bone and the delivery of PDGF-BB to the joint cavity need to be further explored. In this study, we used sodium hyaluronate to deliver PDGF-BB (SH-PDGF) to the joint space and aimed to determine the mechanisms of SH-PDGF in repairing cartilage and subchondral bone and stabilising the cartilage microenvironment. In this research, we determined the pharmacokinetics of PDGF-BB and SH-PDGF in cartilage. Moreover, we investigated the effects of PDGF-BB and SH-PDGF on cartilage and the subchondral bone microenvironment by identifying changes in the HIF-VEGF-Notch axis and SDF-1-CXCR4 axis in an OA rat model. The results showed that PDGF-BB increased cell viability, decreased HIF-1α levels, inhibited inflammation and improved matrix metabolism in osteoarthritic chondrocytes under hyperoxic or hypoxic conditions. We also found that PDGF-BB and SH-PDGF showed similar effects on repairing cartilage and subchondral bone simultaneously. However, SH-PDGF had some advantages over PDGF-BB in prolonging the injection interval and decreasing the injection time. These protective effects were mediated by the inhibition of both the HIF-1α-VEGF-Notch axis and the SDF-1-CXCR4 axis. The underlying mechanisms include the inhibition of HIF-1α-VEGF-Notch-mediated vessel invasion and SDF-1-CXCR4 axis-mediated crosstalk between cartilage and subchondral tissue.
软骨和软骨下骨的慢性退行性变导致软骨微环境不稳定，这是老年人骨关节炎（OA）发病的关键因素。软骨和软骨下骨的同步修复可能是OA治疗的关键策略。血小板衍生生长因子BB（PDGF-BB）可有效促进软骨细胞再生和血管生成。然而，PDGF-BB影响软骨下骨的机制以及将PDGF-BB递送至关节腔的方法仍有待进一步探索。在本研究中，我们使用透明质酸钠将PDGF-BB（SH-PDGF）递送至关节腔，旨在确定SH-PDGF修复软骨和软骨下骨以及稳定软骨微环境的机制。在本研究中，我们测定了PDGF-BB和SH-PDGF在软骨中的药代动力学。此外，我们通过识别OA大鼠模型中缺氧诱导因子-血管内皮生长因子-Notch轴（HIF-VEGF-Notch轴）和基质细胞衍生因子-1-趋化因子受体4轴（SDF-1-CXCR4轴）的变化，研究了PDGF-BB和SH-PDGF对软骨及软骨下骨微环境的影响。结果表明，在高氧或低氧条件下，PDGF-BB可提高骨关节炎软骨细胞的活力，降低缺氧诱导因子-1α（HIF-1α）水平，抑制炎症反应并改善基质代谢。我们还发现，PDGF-BB和SH-PDGF在同时修复软骨和软骨下骨方面具有相似的作用。然而，SH-PDGF在延长注射间隔和减少注射次数方面比PDGF-BB具有一定优势。这些保护作用是通过抑制HIF-1α-VEGF-Notch轴和SDF-1-CXCR4轴介导的。其潜在机制包括抑制HIF-1α-VEGF-Notch介导的血管侵入以及SDF-1-CXCR4轴介导的软骨与软骨下组织之间的相互作用。
