Anti-Inflammatory and Chondroprotective Effects of Platelet-Derived Growth Factor-BB on Osteoarthritis Rat Models

Abstract

\n Background: It has been proved that PDGF-BB could protect the chondrocytes via multiple mechanisms. The present study aims to further investigating the anti-inflammatory and chondroprotective effects of platelet-derived growth factor (PDGF)-BB on osteoarthritis (OA).Methods: We established an osteoarthritis model in Sprague-Dawley rats through intraarticular injection of 3 mg/50 µL monosodium iodoacetate (MIA). The effects of PDGF-BB on MIA-induced OA were assessed by histopathological staining, real-time PCR, and western blotting. Chondrocytes were transfected with or without SOX-9 siRNA, induced by MIA and treated with PDGF-BB, and cell viability, proinflammatory cytokines, and specific markers were analyzed. For mechanistic analysis, the expression of p-SOX-9/SOX-9, p-RunX-2/RunX-2, and p-PKA/PKA and activation of the JAK2/STAT3, PI3K/AKT, and p38 pathways were analyzed.Results: PDGF-BB significantly inhibited the degeneration of cartilage in MIA-induced OA with reductions in proinflammatory cytokines (IL-1, IL-6, collagen Ⅹ, MMPs and ADATMS) and increases in collagen II, aggrecan, and integrin α5β1, and these effects could be reversed by a PDGFR-β antagonist. Consistently, the in vitro results showed similar effects. PDGF-BB treatment suppressed the activation of the JAK2/STAT3, PI3K/AKT, and p38 signaling pathways after MIA induction in both cartilage and chondrocytes. In addition, activation of PKA by PDGF-BB enhanced SOX-9 phosphorylation, which increased anabolic activity, and attenuated RunX-2 phosphorylation, which decreased catabolic activity. The PKA inhibitor and SOX-9 siRNA suppressed PDGF-BB-mediated chondroprotection.Conclusions: PDGF-BB could attenuate OA development by regulating the JAK2/STAT3 PI3K/AKT and p38 signaling pathways by inhibiting inflammation and enhancing cell proliferation via PKA-mediated regulation of SOX-9/RunX-2.