Department of Orthopedic Surgery, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Zhejiang, China.
School of Basic Medical Sciences & Forensic Medicine, Hangzhou Medical College, Zhejiang, China.
Biomed Res Int. 2022 Aug 4;2022:3215461. doi: 10.1155/2022/3215461. eCollection 2022.
The study of chondrogenic progenitor cells (CPCs) as seed cells has become a new focus of cartilage regeneration. The inflammatory environment of osteoarthritis (OA) inhibits the repair ability of CPCs. But the OA patients' CPCs showed an excellent regeneration ability with intermittent hydrostatic pressure (IHP). However, the mechanism is unclear. We compared the expression of the Hippo signaling effect factor YAP between OA and normal cartilages. Then, the relationship between the Kellgren-Lawrence (K-L) score of OA and the rate of YAP-positive cells was analyzed. The changes of CPCs after IHP and IL-1 applications were observed. The OA model was established by cutting the anterior cruciate ligament of rats. The knee joint of the OA rats was distracted by hinged external fixator to create suitable IHP, named as the IHP group. The IHP group plus intra-articular injection of Verteporfin (VP) was named as the IHP+VP group, and the untreated rat group was named as the CON group. Four and 8 weeks after the operation, the reparative effect was evaluated by MASSON staining and immunohistochemical staining. Lower levels of YAP1 and higher expressions of p-YAP1 were found in the OA group as compared to the normal group. IHP inhibited the Hippo signaling in an inflammatory environment and promoted the proliferation of CPCs. The cartilage deterioration in the CON group progressed more significantly than that in the IHP+VP group. The best reparative effect was observed in the IHP group with increased expression of YAP1 and decreased p-YAP1. These results hint that mechanical stress can activate CPCs and promote cartilage repair in an inflammatory environment through inhibiting Hippo signaling.
软骨祖细胞（CPCs）作为种子细胞的研究已成为软骨再生的新焦点。骨关节炎（OA）的炎症环境抑制了 CPCs 的修复能力。但 OA 患者的 CPCs 在间歇静压（IHP）下表现出优异的再生能力。然而，其机制尚不清楚。我们比较了 OA 和正常软骨中 Hippo 信号效应因子 YAP 的表达。然后，分析了 OA 的 Kellgren-Lawrence（K-L）评分与 YAP 阳性细胞率之间的关系。观察了 IHP 和 IL-1 应用后 CPCs 的变化。通过切断大鼠前交叉韧带建立 OA 模型。用铰链式外固定器对 OA 大鼠的膝关节进行牵引，产生合适的 IHP，命名为 IHP 组。IHP 组加关节内注射 Verteporfin（VP）命名为 IHP+VP 组，未治疗的大鼠组命名为 CON 组。术后 4 周和 8 周，通过 MASSON 染色和免疫组织化学染色评估修复效果。与正常组相比，OA 组 YAP1 水平较低，p-YAP1 表达较高。IHP 在炎症环境中抑制 Hippo 信号，促进 CPCs 的增殖。CON 组的软骨退变比 IHP+VP 组更明显。IHP 组 YAP1 表达增加，p-YAP1 表达减少，修复效果最佳。这些结果提示机械应激可以通过抑制 Hippo 信号激活 CPCs，并在炎症环境中促进软骨修复。
