Lu Ye, Zhang Chengyuan, Jiang Shilin, Yuan Feng
Department of Sports Medicine, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, 600 Yishan Road, Shanghai 200233, China.
Department of Orthopedic Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, 600 Yishan Road, Shanghai 200233, China.
Evid Based Complement Alternat Med. 2022 Mar 2;2022:5019920. doi: 10.1155/2022/5019920. eCollection 2022.
Osteoarthritis is a common degenerative joint disease that can cause pain and disability in patients. There is still a lack of effective treatments to improve pathological changes of osteoarthritis cartilages and reverse the progression of osteoarthritis. Our study aimed to investigate the role of Dlx5 in papain-induced osteoarthritis. Osteoarthritis was induced through intraarticular injection of papain. The pathological damage of cartilage tissues was analyzed by H&E staining. The apoptosis of cartilage tissues was detected by TUNEL assay. Immunohistochemical staining was performed to detect DLX5 and BMP-2. Western blot was performed to detect the expressions of SP7, caspase-3, and MYC. The results showed that administration of anti-Dlx5 improved pathological changes of osteoarthritis cartilages, characterized by decreased chondrocyte proliferation, chondrocyte hypertrophy, and matrix damage. Anti-Dlx5 treatment decreased the expressions of BMP-2 and SP7, which are positive regulators of chondrocyte hypertrophy. Moreover, MYC and caspase-3, the critical mediators for chondrocyte apoptosis, were both decreased after anti-Dlx5 treatment. In conclusion, anti-Dlx5 retarded the progression of osteoarthritis by downregulating chondrocyte hypertrophy and chondrocyte apoptosis-related genes. Our findings suggests that Dlx5 is a promising target for osteoarthritis treatment.
骨关节炎是一种常见的退行性关节疾病,可导致患者疼痛和残疾。目前仍缺乏有效的治疗方法来改善骨关节炎软骨的病理变化并逆转骨关节炎的进展。我们的研究旨在探讨Dlx5在木瓜蛋白酶诱导的骨关节炎中的作用。通过关节内注射木瓜蛋白酶诱导骨关节炎。采用苏木精-伊红(H&E)染色分析软骨组织的病理损伤。采用TUNEL法检测软骨组织的细胞凋亡。进行免疫组织化学染色以检测DLX5和骨形态发生蛋白-2(BMP-2)。采用蛋白质免疫印迹法检测SP7、半胱天冬酶-3(caspase-3)和MYC的表达。结果表明,给予抗Dlx5可改善骨关节炎软骨的病理变化,其特征为软骨细胞增殖减少、软骨细胞肥大和基质损伤。抗Dlx5治疗降低了软骨细胞肥大的正调节因子BMP-2和SP7的表达。此外,抗Dlx5治疗后,软骨细胞凋亡的关键介质MYC和caspase-3均降低。总之,抗Dlx5通过下调软骨细胞肥大和软骨细胞凋亡相关基因延缓了骨关节炎的进展。我们的研究结果表明,Dlx5是骨关节炎治疗的一个有前景的靶点。