Department of Orthopaedics, Peking University Third Hospital, Beijing 100191, China.
Engineering Research Center of Bone and Joint Precision Medicine, Ministry of Education, Beijing 100191, China.
J Proteome Res. 2024 Feb 2;23(2):738-748. doi: 10.1021/acs.jproteome.3c00584. Epub 2024 Jan 11.
Osteoarthritis (OA) is a prevalent debilitating whole-joint disorder. Currently, a growing number of proteomic studies have been performed to evaluate molecular biomarkers in several tissues from OA patients; however, little is known about the protein profiles in subchondral bone of OA. In this study, proteomic analysis was performed on subchondral bone from patients with OA to identify differentially expressed proteins (DEPs). Bioinformatics tools were used to further investigate these DEPs. Thereafter, DEPs were validated in the samples from patients with OA, as well as in bilateral ovariectomy-induced OA (OVX-OA) rats using immunohistochemistry. A comprehensive subchondral bone proteome profile of patients with OA was constructed. Additionally, biological information analysis showed that a majority of DEPs participated in the dysregulation of the complement and coagulation cascades. The validation experiments suggested that SerpinA5, the protein involved in the complement and coagulation cascades, was significantly increased in severely damaged subchondral bone of patients with OA compared to the control group. Furthermore, the increase of SerpinA5 in OVX-OA rats compared to control rats was also confirmed. Our results indicated that the dysregulation of coagulation and complement pathways plays a role in the progression of OA, and it provides a promising therapeutic target of OA.
骨关节炎（OA）是一种普遍存在的使人衰弱的全关节疾病。目前，已经进行了越来越多的蛋白质组学研究，以评估 OA 患者几种组织中的分子生物标志物；然而，关于 OA 患者软骨下骨中的蛋白质谱知之甚少。在这项研究中，对 OA 患者的软骨下骨进行了蛋白质组学分析，以鉴定差异表达蛋白（DEPs）。使用生物信息学工具进一步研究了这些 DEPs。之后，使用免疫组织化学在 OA 患者以及双侧卵巢切除诱导的 OA（OVX-OA）大鼠的样本中验证了 DEPs。构建了 OA 患者的全面软骨下骨蛋白质组图谱。此外，生物信息分析表明，大多数 DEPs 参与了补体和凝血级联的失调。验证实验表明，与对照组相比，OA 患者严重受损的软骨下骨中涉及补体和凝血级联的 SerpinA5 蛋白显著增加。此外，还证实了 OVX-OA 大鼠中 SerpinA5 的增加与对照组大鼠相比。我们的结果表明，凝血和补体途径的失调在 OA 的进展中起作用，并为 OA 的治疗提供了有前途的靶点。
