title: Hyaluronic Acid Suppresses the Expression of Metalloproteinases in Osteoarthritic Cartilage Stimulated Simultaneously by Interleukin 1β and Mechanical Load.
abstract: OBJECTIVE
  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 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Orthopedic Surgery, Klinikum rechts der Isar, Technical University Munich, Ismaninger Str, 22, 81675 Munich, Germany.
authors.forename: Florian
authors.initials: F
authors.lastname: Pohlig
authors.affiliation: Department of Orthopedic Surgery, Klinikum rechts der Isar, Technical University Munich, Ismaninger Str, 22, 81675 Munich, Germany.
authors.forename: Florian
authors.initials: F
authors.lastname: Guell
authors.affiliation: Department of Traumatology, Universitätsspital Basel, Spitalstr. 21, 4031 Basel, Switzerland.
authors.forename: Ulrich
authors.initials: U
authors.lastname: Lenze
authors.affiliation: Department of Orthopedic Surgery, Klinikum rechts der Isar, Technical University Munich, Ismaninger Str, 22, 81675 Munich, Germany.
authors.forename: Florian W
authors.initials: FW
authors.lastname: Lenze
authors.affiliation: Department of Orthopedic Surgery, Klinikum rechts der Isar, Technical University Munich, Ismaninger Str, 22, 81675 Munich, Germany.
authors.forename: Heinrich M L
authors.initials: HM
authors.lastname: Mühlhofer
authors.affiliation: Department of Orthopedic Surgery, Klinikum rechts der Isar, Technical University Munich, Ismaninger Str, 22, 81675 Munich, Germany.
authors.forename: Johannes
authors.initials: J
authors.lastname: Schauwecker
authors.affiliation: Department of Orthopedic Surgery, Klinikum rechts der Isar, Technical University Munich, Ismaninger Str, 22, 81675 Munich, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Toepfer
authors.affiliation: Department of Orthopedic Surgery, Klinikum rechts der Isar, Technical University Munich, Ismaninger Str, 22, 81675 Munich, Germany.
authors.forename: Philipp
authors.initials: P
authors.lastname: Mayer-Kuckuk
authors.affiliation: Department of Orthopedic Surgery, Klinikum rechts der Isar, Technical University Munich, Ismaninger Str, 22, 81675 Munich, Germany.
authors.forename: Rüdiger
authors.initials: R
authors.lastname: von Eisenhart-Rothe
authors.affiliation: Department of Orthopedic Surgery, Klinikum rechts der Isar, Technical University Munich, Ismaninger Str, 22, 81675 Munich, Germany.
authors.forename: Rainer
authors.initials: R
authors.lastname: Burgkart
authors.affiliation: Division of Lower Extremity Surgery, Schulthess Klinik, Lengghalde 2, 8008 Zurich, Switzerland.
authors.forename: Gian M
authors.initials: GM
authors.lastname: Salzmann
mesh_terms: D001696:Biomechanical Phenomena; D002358:Cartilage, Articular / Q000201:enzymology*; D004790:Enzyme Induction; D004794:Enzyme Repression; D015870:Gene Expression; D006801:Humans; D006820:Hyaluronic Acid / Q000494:pharmacology / Q000502:physiology*; D053583:Interleukin-1beta / Q000502:physiology*; D020781:Matrix Metalloproteinase 1 / Q000235:genetics / Q000378:metabolism; D053509:Matrix Metalloproteinase 13 / Q000235:genetics / Q000378:metabolism*; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000378:metabolism; D040542:Mechanotransduction, Cellular; D010003:Osteoarthritis / Q000201:enzymology*
chemical_list: C508585:IL1B protein, human; D053583:Interleukin-1beta; D006820:Hyaluronic Acid; C507079:MMP13 protein, human; D053509:Matrix Metalloproteinase 13; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2; C522360:MMP1 protein, human; D020781:Matrix Metalloproteinase 1