Hyaluronic Acid Suppresses the Expression of Metalloproteinases in Osteoarthritic Cartilage Stimulated Simultaneously by Interleukin 1β and Mechanical Load.
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...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
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Public Library of Science (PLoS)
2016-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC4774918?pdf=render |
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| author | Florian Pohlig Florian Guell Ulrich Lenze Florian W Lenze Heinrich M L Mühlhofer Johannes Schauwecker Andreas Toepfer Philipp Mayer-Kuckuk Rüdiger von Eisenhart-Rothe Rainer Burgkart Gian M Salzmann |
| author_facet | Florian Pohlig Florian Guell Ulrich Lenze Florian W Lenze Heinrich M L Mühlhofer Johannes Schauwecker Andreas Toepfer Philipp Mayer-Kuckuk Rüdiger von Eisenhart-Rothe Rainer Burgkart Gian M Salzmann |
| author_sort | Florian Pohlig |
| collection | DOAJ |
| description | 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.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.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 of MMP-13 expression in grade IV as compared to grade II OA. In contrast to the observed MMP-13 suppression, treatment with HA resulted in a suppression of MMP-1 expression only at 1 mg/ml HA, while MMP-2 expression was not significantly affected by either HA concentration.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 may benefit the development of treatment strategies aimed at blocking tissue degradation in OA patients. |
| first_indexed | 2024-12-11T22:16:48Z |
| format | Article |
| id | doaj.art-ec4a2f306f26451387d6151db629f6ee |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-11T22:16:48Z |
| publishDate | 2016-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-ec4a2f306f26451387d6151db629f6ee2022-12-22T00:48:35ZengPublic Library of Science (PLoS)PLoS ONE1932-62032016-01-01113e015002010.1371/journal.pone.0150020Hyaluronic Acid Suppresses the Expression of Metalloproteinases in Osteoarthritic Cartilage Stimulated Simultaneously by Interleukin 1β and Mechanical Load.Florian PohligFlorian GuellUlrich LenzeFlorian W LenzeHeinrich M L MühlhoferJohannes SchauweckerAndreas ToepferPhilipp Mayer-KuckukRüdiger von Eisenhart-RotheRainer BurgkartGian M SalzmannIn 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.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.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 of MMP-13 expression in grade IV as compared to grade II OA. In contrast to the observed MMP-13 suppression, treatment with HA resulted in a suppression of MMP-1 expression only at 1 mg/ml HA, while MMP-2 expression was not significantly affected by either HA concentration.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 may benefit the development of treatment strategies aimed at blocking tissue degradation in OA patients.http://europepmc.org/articles/PMC4774918?pdf=render |
| spellingShingle | Florian Pohlig Florian Guell Ulrich Lenze Florian W Lenze Heinrich M L Mühlhofer Johannes Schauwecker Andreas Toepfer Philipp Mayer-Kuckuk Rüdiger von Eisenhart-Rothe Rainer Burgkart Gian M Salzmann Hyaluronic Acid Suppresses the Expression of Metalloproteinases in Osteoarthritic Cartilage Stimulated Simultaneously by Interleukin 1β and Mechanical Load. PLoS ONE |
| title | Hyaluronic Acid Suppresses the Expression of Metalloproteinases in Osteoarthritic Cartilage Stimulated Simultaneously by Interleukin 1β and Mechanical Load. |
| title_full | Hyaluronic Acid Suppresses the Expression of Metalloproteinases in Osteoarthritic Cartilage Stimulated Simultaneously by Interleukin 1β and Mechanical Load. |
| title_fullStr | Hyaluronic Acid Suppresses the Expression of Metalloproteinases in Osteoarthritic Cartilage Stimulated Simultaneously by Interleukin 1β and Mechanical Load. |
| title_full_unstemmed | Hyaluronic Acid Suppresses the Expression of Metalloproteinases in Osteoarthritic Cartilage Stimulated Simultaneously by Interleukin 1β and Mechanical Load. |
| title_short | Hyaluronic Acid Suppresses the Expression of Metalloproteinases in Osteoarthritic Cartilage Stimulated Simultaneously by Interleukin 1β and Mechanical Load. |
| title_sort | hyaluronic acid suppresses the expression of metalloproteinases in osteoarthritic cartilage stimulated simultaneously by interleukin 1β and mechanical load |
| url | http://europepmc.org/articles/PMC4774918?pdf=render |
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