Evaluation of serum biomarkers after intra-articular injection of rat bone marrow-derived mesenchymal stem cells in a rat model of knee osteoarthritis

Background: Osteoarthritis (OA) is a prevalent joint disorder characterized by joint pain, functional impairment, and disability. The current study investigated the therapeutic effects of intra-articular injection of rat bone marrow-derived mesenchymal stem cells (rBM-MSCs) in rats with knee OA.

Methods: Fourty five male Wistar rats were randomly divided into three groups (A-C) and received either an intra-articular injection of normal saline (NS) or rBM-MSCs. The normal control group (A, n = 15) received NS, the OA control group (B, n = 15) received NS, and the OA treated group (C, n = 15) received rBM-MSCs (0.5 × 10⁶ cells in 25 μL NS). Knee OA was induced using monosodium iodoacetate (MIA). rBM-MSCs were sourced from female Wistar rats and their stem cells were characterized using flow cytometry. Histomorphometric analyses were performed on knee sections from both normal and OA knee. Serum biomarkers, including hyaluronic acid (HA), cross-linked N-telopeptide of type I collagen-1 (NTX-1), NGF, calcitonin gene-related peptide (CGRP), matrix metalloproteinase-3 (MMP-3), oligomeric cartilage matrix protein COMP, interleukin-6 (IL-6), and soluble IL-6 receptor (sIL-6R), were analyzed using ELISA kits. Ingenuity Pathway Analysis (IPA) was used to determine the genes regulated by MSCs in OA, and the protective mechanisms were determined using the Molecular Activity Predictor (MAP).

Results: rBM-MSCs were positive for CD29 and CD90 and negative for CD45 surface markers. OA biomarkers were significantly elevated in the untreated OA group but decreased after treatment with intra-articular MSCs. The OA group treated with MSCs showed significant repair of the damaged cartilage compared to the control group.

Conclusions: Cartilage damage leads to an increase in inflammatory cytokine levels and is associated with an increase in serum biomarkers related to cartilage degradation. Intra-articular administration of MSCs showed beneficial effects, including regeneration of damaged cartilage and a reduction in inflammation-related serum biomarker levels.