MSC-derived exosomes promote chondrocyte proliferation and inhibit apoptosis by suppressing inflammation in osteoarthritis

Background: Osteoarthritis (OA) is marked by reduced chondrocyte proliferation, increased Apoptosis, and an inflammatory microenvironment. Mesenchymal stem cell-derived Exosomes (MSC-Exos) are promising modulators of chondrocyte function; however, their precise roles remain unclear. This study explores whether MSC-Exos protect chondrocytes from IL-1β-induced injury via these effects, in vitro and in a rat OA model.

Methods: BMSC-derived Exosomes (BMSC-Exos) were isolated via ultracentrifugation and characterized (TEM, NTA, Western blotting). Chondrocyte injury was induced by IL-1β (10 ng/mL). Effects of BMSC-Exos on proliferation (CCK-8), Apoptosis (Annexin V/PI), migration (wound healing/Transwell), inflammatory cytokines (ELISA), and NF-κB p65 phosphorylation (Western blotting) were evaluated. In vivo, OA was induced by intra-articular sodium iodoacetate in rats, and MSC-Exos were administered weekly. Histological Staining (H&E and Safranin O-Fast Green) was performed to assess cartilage repair, immunohistochemical (IHC) analysis for IL-1β, TNF-α, IL-6, type II Collagen and aggrecan was conducted, and analysis of p65 phosphorylation in cartilage tissue was conducted.

Results: BMSC-Exos significantly increased chondrocyte proliferation, reduced Apoptosis, suppressed TNF-α, IL-6, and IL-1β expression, and inhibited p65 phosphorylation in vitro. In vivo, BMSC-Exos attenuated cartilage erosion, subchondral bone exposure, synovial hyperplasia and inflammatory cell infiltration. IHC analysis demonstrated that BMSC-Exos treatment significantly reduced the expression of IL-1β, TNF-α, IL-6, while restoring the levels of cartilage matrix components in cartilage compared to the OA model group. Reduced phospho-p65 levels correlated with these histological and molecular improvements.

Conclusion: MSC-Exos protect chondrocytes from inflammatory injury via promoting proliferation, inhibiting Apoptosis, reducing inflammation, and suppressing NF-κB, with therapeutic potential for OA.