Abstract
Osteoarthritis (OA) of the knee is a debilitating condition that can severely limit an individual's mobility and quality of life. This study was designed to evaluate the efficacy of bone marrow-derived mesenchymal stem cell (BM-MSC) treatment in cartilage repair using a rat model of monoiodoacetate- (MIA-) induced knee OA. OA was induced in the knee joint of rats by an intracapsular injection of MIA (2 mg/50 mu L) on day zero. The rats were divided into three groups (n=6): a normal control group, an osteoarthritic control group, and an osteoarthritic group receiving a single intra-articular injection of BM-MSCs (5x106 cells/rat). The knee diameter was recorded once per week. By the end of the performed experiment, X-ray imaging and enzyme-linked immunosorbent assay analysis of serum inflammatory cytokines interleukin-1beta (IL-beta), IL-6, and tumor necrosis factor-alpha (TNF-alpha) and anti-inflammatory cytokines interleukin-10 and transforming growth factor-beta (TGF-beta) were carried out. In addition, RT-PCR was used to measure nuclear factor-kappa B (NF-kappa B), inducible nitric oxide synthase (iNOS), and type II collagen mRNA levels and Western blot analysis was used to determine caspase-3 protein levels in all treated groups. Finally, hematoxylin/and eosin stains were used for histopathological investigation. Administration of BM-MSCs significantly downregulated knee joint swelling and MIA-induced (IL-1 beta, IL-6, and TNF-alpha) and upregulated IL-10 and TGF-beta as well. Moreover, BM-MSC-treated osteoarthritic rats exhibited decreased expression of NF-kappa B, iNOS, and apoptotic mediator (caspase-3) and increased expression of type II collagen when compared to rats treated with MIA alone. The hematoxylin/eosin-stained sections revealed that BM-MSC administration ameliorated the knee joint alterations in MIA-injected rats. BM-MSCs could be an effective treatment for inflamed knee joints in the MIA-treated rat model of osteoarthritis, and the effect may be mediated via its anti-inflammatory and antioxidant potential.