Anti­inflammatory and anti­catabolic effect of non­animal stabilized hyaluronic acid and mesenchymal stem cell­conditioned medium in an osteoarthritis coculture model.

ABSTRACT

Previous clinical studies have reported the clinical effectiveness of non­animal stabilized hyaluronic acid (NASHA) and adipose­derived mesenchymal stromal/stem cells (MSC) in the treatment of knee osteoarthritis (OA). Unlike MSC secreted mediators, in vitro anti­inflammatory effects of NASHA have not been evaluated. We aimed to evaluate and compare the anti­inflammatory effect of NASHA and MSC conditioned medium (stem cell­conditioned medium; SC­CM), in an explant­based coculture model of OA. Cartilage and synovial membrane from seven patients undergoing total knee arthroplasty were used to create a coculture system. Recombinant IL­1ß was added to the cocultures to induce inflammation. Four experimental groups were generated i) Basal; ii) IL­1ß; iii) NASHA (NASHA + IL­1ß); and iv) SC­CM (SC­CM + IL­1ß). Glycosaminoglycans (GAG) released in the culture medium and of nitric oxide (NO) production were quantified. Gene expression in cartilage and synovium of IL­1ß, matrix metallopeptidase 13 (MMP13), ADAM metallopeptidase with thrombospondin type 1 motif 5 (ADAMTS5) and tissue inhibitor of metalloproteinases 1 (TIMP1) was measured by reverse transcription­quantitative PCR. Media GAG concentration was decreased in cocultures with NASHA and SC­CM (48 h, P<0.05; 72 h, P<0.01) compared with IL­1ß. Production of NO was significantly lower only in SC­CM after 72 h (P<0.01). In cartilage, SC­CM inhibited the expression of IL­1ß, MMP13 and ADAMTS5, while NASHA had this effect only in MMP13 and ADAMTS5. In synovium, SC­CM decreased the expression level of MMP13 and ADAMTS5, while NASHA only decreased ADAMTS5 expression. Both NASHA and SC­CM increased TIMP1 expression in cartilage and synovium. Treatments with NASHA and SC­CM were shown to be a therapeutic option that may help counteract the catabolism produced by the inflammatory state in knee OA. The anti­inflammatory mediators produced by MSC promote a lower expression of inflammatory targets in our study model.