Intra-articular resveratrol injection prevents osteoarthritis progression in a mouse model by activating SIRT1 and thereby silencing HIF-2α.
We investigated the feasibility of the intra-articular injection of resveratrol for preventing the progression of existing cartilage degeneration in a mouse model of osteoarthritis (OA). The effects of resveratrol on the expression of silent information regulator 2 type 1 (SIRT1), hypoxia-inducible factor-2α (HIF-2α) and catabolic factors in OA cartilage was explored. OA was induced in the mouse knee via destabilization of the medial meniscus (DMM). Resveratrol was injected weekly into the operated knee beginning 4 weeks after surgery. The OA phenotype was evaluated via histological and immunohistochemical analyses at 8 weeks after DMM. Western blot analysis was performed to identify whether resveratrol modulated the interleukin (IL)-1β-induced expression of HIF-2α in human chondrocytes. Histologically, resveratrol treatment preserved the structural homeostasis of the articular cartilage and the subchondral bone. Following resveratrol injection, the expression of collagen type II was retained, but the expression of inducible nitric oxide synthase and matrix metalloproteinase-13 was reduced in OA cartilage. Moreover, the administration of resveratrol significantly induced the activation of SIRT1 and the inhibition of HIF-2α expression in mouse OA cartilage and in IL-1β-treated human chondrocytes. These findings indicate that the intra-articular injection of resveratrol significantly prevents the destruction of OA cartilage by activating SIRT1 and thereby suppressing the expression of HIF-2α and catabolic factors.
Department of Orthopedic Surgery, Luoyang Orthopedic-Traumatological Hospital, Henan, PR, China.
Wuyin
W
Li
Department of Orthopedic Surgery, Luoyang Orthopedic-Traumatological Hospital, Henan, PR, China.
Litao
L
Cai
Institute of Arthritis Research, Shanghai Academy of Chinese Medical Sciences and Guanghua Integrative Medicine Hospital, Shanghai, PR, China.
Yun
Y
Zhang
Department of Plastic and Reconstructive Surgery, Shanghai Ninth People's Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, PR, China.
Lei
L
Cui
Department of Plastic and Reconstructive Surgery, Second Affiliated Hospital, Nanjing Medical University, Nanjing, PR, China.
Gan
G
Shen
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology / Q000627:therapeutic use*; D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism*; D002358:Cartilage, Articular / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D024043:Collagen Type II / Q000378:metabolism; D004353:Drug Evaluation, Preclinical; D007270:Injections, Intra-Articular; D008297:Male; D053509:Matrix Metalloproteinase 13 / Q000378:metabolism; D008810:Mice, Inbred C57BL; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D010003:Osteoarthritis / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D008517:Phytotherapy; D011897:Random Allocation; D000077185:Resveratrol; D056564:Sirtuin 1 / Q000378:metabolism*; D013267:Stilbenes / Q000494:pharmacology / Q000627:therapeutic use*; D000099162:Endothelial PAS Domain-Containing Protein 1
D000975:Antioxidants; D051792:Basic Helix-Loop-Helix Proteins; D024043:Collagen Type II; D053509:Matrix Metalloproteinase 13; D052247:Nitric Oxide Synthase Type II; D000077185:Resveratrol; D056564:Sirtuin 1; D013267:Stilbenes; D000099162:Endothelial PAS Domain-Containing Protein 1; C496317:Nos2 protein, mouse; C507081:Mmp13 protein, mouse; C470545:Sirt1 protein, mouse
HIF-2α; SIRT1; catabolic factor; osteoarthritis; resveratrol