Assessment of the Efficacy of Bone Marrow-Derived Mesenchymal Stem Cells against a Monoiodoacetate-Induced Osteoarthritis Model in Wistar Rats

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 μL) on day zero. The rats were divided into three groups ( <a:math xmlns:a="http://www.w3.org/1998/Math/MathML" id="M1"> <a:mi>n</a:mi> <a:mo>=</a:mo> <a:mn>6</a:mn> </a:math> ): a normal control group, an osteoarthritic control group, and an osteoarthritic group receiving a single intra-articular injection of BM-MSCs ( <c:math xmlns:c="http://www.w3.org/1998/Math/MathML" id="M2"> <c:mn>5</c:mn> <c:mo>×</c:mo> <c:msup> <c:mrow> <c:mn>10</c:mn> </c:mrow> <c:mrow> <c:mn>6</c:mn> </c:mrow> </c:msup> </c:math> 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-β), IL-6, and tumor necrosis factor-α (TNF-α) and anti-inflammatory cytokines interleukin-10 and transforming growth factor-beta (TGF-β) were carried out. In addition, RT-PCR was used to measure nuclear factor-kappa B (NF-κB), 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-1β, IL-6, and TNF-α) and upregulated IL-10 and TGF-β as well. Moreover, BM-MSC-treated osteoarthritic rats exhibited decreased expression of NF-κB, 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.

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