Effects of ID-CBT5101 in Preventing and Alleviating Osteoarthritis Symptoms in a Monosodium Iodoacetate-Induced Rat Model

Abstract

Osteoarthritis is a disease that affects the articular cartilage and osseous tissue, and can be worsened by aging, overweight status, and post-traumatic arthritis. The present study aimed to evaluate the effect of ID-CBT5101 (tyndallized <i>Clostridium butyricum</i>) on bone metabolism and the inflammatory response in a monosodium iodoacetate-induced rat model of osteoarthritis. ID-CBT5101 was administered orally at doses of 10⁸ or 10¹⁰ CFU/day for 2 weeks before direct injection of monosodium iodoacetate (3 mg/50 μl of 0.9% saline) into the intra-articular space of the rats' right knees. The rats subsequently received the same doses of oral ID-CBT5101 for another 4 weeks. We evaluated the treatment effects based on serum biomarkers, mRNA expression, morphological and histopathological analyses of the knee joints, and weight-bearing distribution analysis. Compared with those in control rats, the ID-CBT5101 treatments significantly reduced the serum concentration of inflammation and bone metabolism markers (<i>i.e</i>., COX-2, IL-6, LTB₄, and COMP), and significantly increased the concentration of IFN-γ and glycosaminoglycans. In addition, the ID-CBT5101 treatments inhibited the mRNA expression of matrix metalloproteinases and tissue inhibitors of metalloproteinases (<i>i.e</i>., MMP-2, MMP-3, MMP-9, MMP-13, TIMP-1, and TIMP-2). Furthermore, the ID-CBT5101 treatments effectively preserved the knee cartilage and synovial membrane, and significantly decreased the amount of fibrous tissue. Moreover, compared with that of the negative control group, the ID-CBT5101 treatments increased the weight-bearing distribution by ≥20%. The results indicate that ID-CBT5101 prevented and alleviated osteoarthritis symptoms. Thus, ID-CBT5101 may be a novel therapeutic option for the management of osteoarthritis.