TY - JOUR
T1 - Hyaluronic acid suppresses the expression of metalloproteinases in osteoarthritic cartilage stimulated simultaneously by interleukin 1β and mechanical load
AU - Pohlig, Florian
AU - Guell, Florian
AU - Lenze, Ulrich
AU - Lenze, Florian W.
AU - Mühlhofer, Heinrich M.L.
AU - Schauwecker, Johannes
AU - Toepfer, Andreas
AU - Mayer-Kuckuk, Philipp
AU - Von Eisenhart-Rothe, Rüdiger
AU - Burgkart, Rainer
AU - Salzmann, Gian M.
N1 - Publisher Copyright:
© 2016 Pohlig et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
PY - 2016/3
Y1 - 2016/3
N2 - Purpose In patients with osteoarthritis (OA), intraarticular injection of hyaluronic acid (HA) frequently results in reduced pain and improved function for prolonged periods of time, i.e. more than 6 months. However, the mechanisms underlying these effects are not fully understood. Our underlying hypothesis is that HA modifies the enzymatic breakdown of joint tissues. Methods To test this hypothesis, we examined osteochondral cylinders from 12 OA patients. In a bioreactor, these samples were stimulated by interleukin 1β (Il1ß) (2 ng/ml) plus mechanical load (2.0 Mpa at 0.5 Hz horizontal and 0.1 Hz vertical rotation), thus the experimental setup recapitulated both catabolic and anabolic clues of the OA joint. Results Upon addition of HA at either 1 or 3 mg/ml, we observed a significant suppression of expression of metalloproteinase (MMP)-13. A more detailed analysis based on the Kellgren and Lawrence (K&L) OA grade, showed a much greater degree of suppression ofMMP-13 expression in grade IV as compared to grade II OA. In contrast to the observedMMP-13 suppression, treatment with HA resulted in a suppression ofMMP-1 expression only at 1 mg/ml HA, while MMP-2 expression was not significantly affected by either HA concentration. Conclusion Together, these data suggest that under concurrent catabolic and anabolic stimulation, HA exhibits a pronounced suppressive effect on MMP-13. In the long-run these findings maybenefit the development of treatment strategies aimed at blocking tissue degradation in OA patients.
AB - Purpose In patients with osteoarthritis (OA), intraarticular injection of hyaluronic acid (HA) frequently results in reduced pain and improved function for prolonged periods of time, i.e. more than 6 months. However, the mechanisms underlying these effects are not fully understood. Our underlying hypothesis is that HA modifies the enzymatic breakdown of joint tissues. Methods To test this hypothesis, we examined osteochondral cylinders from 12 OA patients. In a bioreactor, these samples were stimulated by interleukin 1β (Il1ß) (2 ng/ml) plus mechanical load (2.0 Mpa at 0.5 Hz horizontal and 0.1 Hz vertical rotation), thus the experimental setup recapitulated both catabolic and anabolic clues of the OA joint. Results Upon addition of HA at either 1 or 3 mg/ml, we observed a significant suppression of expression of metalloproteinase (MMP)-13. A more detailed analysis based on the Kellgren and Lawrence (K&L) OA grade, showed a much greater degree of suppression ofMMP-13 expression in grade IV as compared to grade II OA. In contrast to the observedMMP-13 suppression, treatment with HA resulted in a suppression ofMMP-1 expression only at 1 mg/ml HA, while MMP-2 expression was not significantly affected by either HA concentration. Conclusion Together, these data suggest that under concurrent catabolic and anabolic stimulation, HA exhibits a pronounced suppressive effect on MMP-13. In the long-run these findings maybenefit the development of treatment strategies aimed at blocking tissue degradation in OA patients.
UR - https://www.scopus.com/pages/publications/84962242422
U2 - 10.1371/journal.pone.0150020
DO - 10.1371/journal.pone.0150020
M3 - Article
C2 - 26934732
AN - SCOPUS:84962242422
SN - 1932-6203
VL - 11
JO - PLoS ONE
JF - PLoS ONE
IS - 3
M1 - e0150020
ER -