PT  - JOURNAL ARTICLE
AU  - Zvezdana Mladenovic
AU  - Anne-Sophie Saurel
AU  - Francis Berenbaum
AU  - Claire Jacques
TI  - Potential Role of Hyaluronic Acid on Bone in Osteoarthritis: Matrix Metalloproteinases, Aggrecanases, and RANKL Expression are Partially Prevented by Hyaluronic Acid in Interleukin 1β–stimulated Osteoblasts
AID  - 10.3899/jrheum.130378
DP  - 2014 Apr 15
TA  - The Journal of Rheumatology
PG  - jrheum.130378
4099  - http://www.jrheum.org/content/early/2014/04/14/jrheum.130378.short
4100  - http://www.jrheum.org/content/early/2014/04/14/jrheum.130378.full
AB  - Objective To determine the effect of hyaluronic acid (HA) on proteolytic enzymes and bone remodeling mediators induced by interleukin 1b (IL-1β) 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 μg/ml HA during the last week of culture, then stimulated with IL-1β (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), osteoprotegerin, and receptor activator of nuclear factor-kB ligand (RANKL) was determined by real-time polymerase chain reaction. MMP-3 and MMP-13 release was assessed by Western blot analysis. Results IL-1β 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-1β-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-1β-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.