Anti-inflammatory and anti-catabolic effect of non-animal stabilized hyaluronic acid and mesenchymal stem cell-conditioned medium in an osteoarthritis coculture model

Abstract

Previous clinical studies have reported the clinical effectiveness of non-animal stabilized hyaluronic acid (naSHa) and adipose-derived mesenchymal stromal/stem cells (MSc) in the treatment of knee osteoarthritis (oa). unlike MSc secreted mediators, in vitro anti-inflammatory effects of naSHa have not been evaluated. We aimed to evaluate and compare the anti-inflammatory effect of NASHA and MSc conditioned medium (stem cell-conditioned medium; Sc-cM), in an explant-based coculture model of oa. cartilage and synovial membrane from seven patients undergoing total knee arthroplasty were used to create a coculture system. recombinant il-1β was added to the cocultures to induce inflammation. Four experimental groups were generated: i) Basal; ii) il-1β; iii) naSHa (naSHa + il-1β); and iv) Sc-cM (Sc-cM + il-1β). Glycosaminoglycans (GaG) released in the culture medium and of nitric oxide (no) production were quantified. Gene expression in cartilage and synovium of IL-1β, matrix metallopeptidase 13 (MMP13), adaM metallopeptidase with thrombospondin type 1 motif 5 (ADAMTS5) and tissue inhibitor of metalloproteinases 1 (TIMP1) was measured by reverse transcription-quantitative Pcr. Media GaG concentration was decreased in cocultures with naSHa and Sc-cM (48 h, P<0.05; 72 h, P<0.01) compared with il-1β. Production of no was significantly lower only in Sc-cM after 72 h (P<0.01). in cartilage, Sc-cM inhibited the expression of IL-1β, MMP13 and ADAMTS5, while naSHa had this effect only in MMP13 and ADAMTS5. in synovium, Sc-cM decreased the expression level of MMP13 and ADAMTS5, while naSHa only decreased ADAMTS5 expression. Both naSHa and Sc-cM increased TIMP1 expression in cartilage and synovium. Treatments with naSHa and Sc-cM were shown to be a therapeutic option that may help counteract the catabolism produced by the inflammatory state in knee OA. The anti-inflammatory mediators produced by MSc promote a lower expression of inflammatory targets in our study model.