Attenuation of inflammation and cartilage degradation by sulfasalazine-containing hyaluronic acid on osteoarthritis rat model

The aim of this study was to investigate the effects of a sulfasalazine-containing hyaluronic acid (SASP/HA) systems on in vitro anti-inflammation and the alleviation of cartilage degradation in both lipopolysaccharide (LPS)-stimulated synoviocytes and a rat model of monosodium iodoacetate (MIA)-induced osteoarthritis (OA). The SASP/HA resulted in long-term release of SASP from the SASP/HA for up to 60 days in a sustained manner. In vitro studies performed using real-time polymerase chain reaction (PCR) assay revealed that the SASP/HA was able to effectively and dose-dependently inhibit the mRNA expression levels of pro-inflammatory cytokines such as matrix metalloproteinases-3 (MMP-3), cyclooxygenase-2 (COX-2), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) in LPS-stimulated synoviocytes. In vivo studies showed that intra articular injection of SASP/HA greatly reduced the MIA-stimulated mRNA expression of MMP-3, COX-2, IL-6, and TNF-α in blood. Furthermore, these significant anti-inflammatory effects of SASP/HA contributed markedly to the alleviation of progression of MIA-induced OA and cartilage degradation, as demonstrated by X-ray, micro-computed tomography (micro-CT), gross findings, and histological evaluations. Therefore, our findings indicated that the long-term and sustained delivery of SASP using HA can play a therapeutic role in alleviating inflammation as well as protecting against cartilage damage in OA.