TSP-1 increases autophagy level in cartilage by upregulating HSP27 which delays progression of osteoarthritis

• Published in: International immunopharmacology Vol. 128; p. 111475
• Main Authors: Li, Haoqian, Huang, Lingan, Zhao, Ruipeng, Wu, Gaige, Yin, Yukun, Zhang, Chengming, Li, Pengcui, Guo, Li, Wei, Xiaochun, Che, Xianda, Li, Lu
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 15.02.2024
• Subjects: Animals; Autophagy; Cartilage, Articular - metabolism; Chondrocytes; Degeneration; Disease Models, Animal; HSP27; HSP27 Heat-Shock Proteins - metabolism; HSP27 Heat-Shock Proteins - pharmacology; Osteoarthritis; Osteoarthritis - metabolism; Proteomics; Rats; Thrombospondin 1 - metabolism; TSP-1; Degeneration; TSP-1; Osteoarthritis; Autophagy; HSP27
• ISSN: 1567-5769; 1878-1705
• DOI: 10.1016/j.intimp.2023.111475

•TSP-1 is downregulated in OA human articular cartilage.•TSP-1 has potential as a biomarker for diagnosing early OA.•TSP-1 suppresses catabolic responses and enhances anabolism in vitro and vivo.•TSP-1 affects autophagy level by upregulating HSP27 to delay OA progression.•TSP-1 promotes chondrocyte proliferation and inhibits apoptosis in vitro and in vivo. This study aimed to determine whether Thrombospondin-1 (TSP-1) can be used as a biomarker to diagnose early osteoarthritis (OA) and whether it has a chondroprotective effect against OA. We examined TSP-1 expression in cartilage, synovial fluid, and serum at different time points after anterior cruciate ligament transection (ACLT) surgery in rats. Subsequently, TSP-1 was overexpressed or silenced to detect its effects on extracellular matrix (ECM) homeostasis, autophagy level, proliferation and apoptosis in chondrocytes. Adenovirus encoding TSP-1 was injected into the knee joints of ACLT rats to test its effect against OA. Combined with proteomic analysis, the molecular mechanism of TSP-1 in cartilage degeneration was explored. Intra-articular injection of an adenovirus carrying the TSP-1 sequence showed chondroprotective effects against OA. Moreover, TSP-1 expression decreases with OA progression and can effectively promote cartilage proliferation, inhibit apoptosis, and helps to sustain the balance between ECM anabolism and catabolism. Overexpression of TSP-1 also can increase autophagy by upregulating Heat Shock Protein 27 (HSP27, hspb1), thereby enhancing its effect as a stimulator of autophagy. TSP-1 is a hopeful strategy for OA treatment.