Potential Role of Hyaluronic Acid on Bone in Osteoarthritis: Matrix Metalloproteinases, Aggrecanases, and RANKL Expression are Partially Prevented by Hyaluronic Acid in Interleukin 1-stimulated Osteoblasts

Objective. To determine the effect of hyaluronic acid (HA) on proteolytic enzymes and bone remodeling mediators induced by interleukin 1 beta (IL-1 beta) and related to cartilage catabolism in murine osteoblasts. Methods. Osteoblasts were obtained from Swiss mice and cultured for 3 weeks. HA-treated osteoblasts were incubated with 100 mu g/ml HA during the last week of culture, then stimulated with IL-1 beta (10 ng/ml) for 24 h. The expression of matrix metalloproteinases 3 and 13 (MMP-3 and MMP-13), ADAMTS-4 and ADAMTS-5, tissue inhibitor of metalloproteinases (TIMP), osteo-protegerin, and receptor activator of nuclear factor-kappa B ligand (RANKL) was determined by real-time polymerase chain reaction. MMP-3 and MMP-13 release was assessed by Western blot analysis. Results. IL-1 beta increased the mRNA levels of MMP-3 and MMP-13 and ADAMTS-4 and ADAMTS-5 and release of MMP-3 and MMP-13. Seven days of HA treatment significantly prevented the IL-1 beta-increased mRNA levels of MMP-3 (-61%, p < 0.01), MMP-13 (-56%, p < 0.01), ADAMTS-4 (-58%, p < 0.05), ADAMTS-5 (-52%, p < 0.01), and RANKL (-49%, p < 0.05), but not TIMP. As well, IL-1 beta-induced production of MMP-3 and MMP-13 was inhibited, by 27% (p < 0.01) and 40% (p < 0.01), respectively. Conclusion. In an inflammatory context in murine osteoblasts, HA can inhibit the expression of MMP and ADAMTS. Because HA can counteract the production of these mediators in chondrocytes, its beneficial effect in osteoarthritis may be due to its action on cartilage and subchondral bone.