Osteoarthritis (OA) is a slowly progressive joint disease typically seen in middle-age to elderly people. At present, there is no ideal agent to treat OA. Chenodeoxycholic acid (CDCA) was a principal active constituent from animal bile. However, the therapeutic effect of CDCA on OA severity was largely unknown. The purpose of this study was to evaluate the therapeutic effect of intra-articular injection of CDCA in a rabbit OA model. OA was induced in experimental rabbits by anterior cruciate ligament transection (ACLT) and then rabbits were intra-articularly injected with CDCA (10?mg/kg or 50?mg/kg) once per week for 5 weeks. The results showed that CDCA significantly decreased cartilage degradation on the surface of femoral condyles, reducing the pathological changes of articular cartilage and synovial membrane by macroscopic and histological analysis. Chenodeoxycholic acid(CDCA) also significantly decreased bone destruction and erosion of joint evaluated by micro-CT. Furthermore, CDCA could markedly reduce the release of matrix metalloproteinase-1 (MMP-1), matrix metalloproteinase-3 (MMP-3), interleukin-1β (IL-1β), and prostaglandin E2 (PGE2) in synovial fluid. These observations highlight chenodeoxycholic acid(CDCA) might be a potential therapeutic agent for OA.

Osteoarthritis (OA) is a prevalent form of arthritic disease and a leading cause of physical disability in adult population. It was generally considered a whole joint disease characterized mainly by cartilage destruction, subchondral bone sclerosis, osteophyte formation, and joint synovitis. Though much research has been performed, the concrete causes of OA remain unclear. At present, OA progression is considered to be regulated largely by an excess of matrix metalloproteinases (MMPs), which contribute to the degradation of the extracellular matrix. Among these enzymes, MMP-1 and MMP-3 play important roles in OA progression by degrading the extracellular matrix. Moreover, inflammatory mediators such as IL-1β and PGE2, have been implicated in the synovial inflammation and cartilage degradation in OA. Levels of IL-1β and PGE2 are increased in the synovial fluid and cartilage of OA patients, implying a role for IL-1β and PGE2 in the pathogenesis of OA.

The currently available pharmacological treatments for OA are effective only temporarily and might result in undesirable gastrointestinal, renal, and cardiovascular side effects. There is an increasing interest in the use of natural compounds extracted from Traditional Chinese Medicine (TCM) for the treatment of OA because they are reported to demonstrate satisfactory clinical efficacy with minimal side effects, compared to routine pharmacological strategies. Our group has previously reported that chenodeoxycholic acid (CDCA) was an important active constituent from animal bile and exhibited obviously inhibitory effect on MMPs in vitro. However, the effect of CDCA on OA severity in vivo has not yet been studied at present. In continuation of our previous study and development of a novel small molecule drug to treat OA, we elucidated the therapeutic effect of chenodeoxycholic acid(CDCA) in an experimental rabbit model of OA for the first time in this paper.