Osteoarthritis (OA) is the most common form of joint disease. Currently, OA treatment is limited to controlling symptoms. Our previous study showed that stromal cell-derived factor 1 (SDF-1) delayed the progression of OA to a certain extent. The aim of this study was to explore the specific mechanism of SDF-1 in OA. OA chondrocytes and a collagen-induced osteoarthritis (CIOA) mouse model were used as in vitro and in vivo models, respectively. SDF-1 was used to treat OA in vitro and in vivo. To explore the mechanism of SDF-1 in OA treatment, we pretreated chondrocytes with a Sirt 3 inhibitor and assessed mitochondrial function and then analysed related indicators of cartilage anabolic and cartilage metabolism. SOD2 and PGC-1α levels were significantly lower in OA chondrocytes and the cartilage of CIOA model mice than in normal chondrocytes, and mitochondrial dysfunction occurred in OA. After treating OA chondrocytes and CIOA model mice with exogenous SDF-1, mitochondrial dysfunction and abnormal biomarkers of OA normalized. The pretreatment of OA chondrocytes with a Sirt 3 inhibitor or mitochondrial function inhibitor before SDF-1 exposure reversed these changes. SDF-1 can alleviate OA by resolving mitochondrial dysfunction through the activation of the Sirt3/PGC-1α signalling pathway, and therefore, SDF-1 may be a good candidate as a new treatment for OA.

Objective: Angiogenesis plays a crucial role in osteoarthritis (OA) by promoting inflammatory cell invasion, supporting neo-innervation and joint tissue fibrosis, and contributing to structural damage and pain. Thrombospondin-3 (THBS-3) is highly expressed in OA cartilage. However, the mechanisms responsible for upregulation of THBS-3 in OA are unclear. Design: OA chondrocytes and a collagen-induced osteoarthritis (CIOA) mouse model were used as in vitro and in vivo models, respectively. THBS-3 was used to treat chondrocytes in vitro and in vivo . To explore the mechanism of THBS-3 in chondrocytes treatment, we pretreated chondrocytes with a THBS-3 inhibitor and assessed cartilage metabolic function and then analyzed related indicators of vascularization and chondrofibrosis. Results: Proteomics revealed higher THBS-3 expression in the cartilage of CIOA mice than in that of normal mice. Compared with those from healthy individuals, chondrocytes from OA patients presented significantly increased protein expression of THBS-3. In both in vivo and in vitro experiments, THBS-3 promoted matrix metalloproteinase-13 and disintegrin and metalloprotease with thrombospondin-5, suppressed aggrecan, and promoted the vascularization and chondrofibrosis in dysfunctional chondrocytes from osteoarthritic chondrocytes. THBS-3 activated the transforming growth factor-beta (TGF-β) signaling pathway. The pretreatment of OA chondrocytes with a TGF-β inhibitor before THBS-3 exposure reversed these changes. Conclusion: THBS-3 promotes the angiogenesis and fibrosis of chondrocytes by activating the TGF-β/Smad2/3 signaling pathway.