Zvezdana Mladenovic1, Anne-Sophie Saurel, Francis Berenbaum, Claire Jacques. 1. From the University Pierre and Marie Curie, Paris; Pierre Fabre Laboratories, Castres; Labex Transimmunomics, DHU i2B, Paris; Department of Rheumatology, AP-HP Saint-Antoine Hospital, Paris, France.
Abstract
OBJECTIVE: To determine the effect of hyaluronic acid (HA) on proteolytic enzymes and bone remodeling mediators induced by interleukin 1β (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-κB 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.
OBJECTIVE: To determine the effect of hyaluronic acid (HA) on proteolytic enzymes and bone remodeling mediators induced by interleukin 1β (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-κB 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.
Authors: Angela Avenoso; Angela D'Ascola; Michele Scuruchi; Giuseppe Mandraffino; Alberto Calatroni; Antonino Saitta; Salvatore Campo; Giuseppe M Campo Journal: Inflamm Res Date: 2017-08-12 Impact factor: 4.575
Authors: Anne-Mari Mustonen; Janne Capra; Kirsi Rilla; Petri Lehenkari; Sanna Oikari; Tommi Kääriäinen; Antti Joukainen; Heikki Kröger; Tommi Paakkonen; Johanna Matilainen; Petteri Nieminen Journal: BMC Musculoskelet Disord Date: 2021-03-06 Impact factor: 2.362