title: Interleukin 17 synergises with tumour necrosis factor alpha to induce cartilage destruction in vitro.
abstract: BACKGROUND
  Interleukin 17 (IL17) is produced by activated T cells and has been implicated in the development of bone lesions and cartilage degradation in rheumatoid arthritis (RA).
  
  
  OBJECTIVE
  To determine whether IL17, alone or together with tumour necrosis factor alpha (TNFalpha), induces cartilage destruction in vitro.
  
  
  METHODS
  Fetal mouse metatarsals stripped of endogenous osteoclast precursors were used to study the effect of IL17 on cartilage degradation independently of osteoclastic resorption. Cartilage destruction was analysed histologically by Alcian blue staining.
  
  
  RESULTS
  IL17 alone, up to 100 ng/ml, had no effect on the cartilage of fetal mouse metatarsals. IL17 (>/=0.1 ng/ml), however, induced severe cartilage degradation when given together with TNFalpha (>/=1 ng/ml). The cytokine combination decreased Alcian blue staining, a marker of proteoglycans, throughout the metatarsals and induced loss of the proliferating and early hypertrophic chondrocyte zones. TNFalpha alone also decreased Alcian blue staining, but not as dramatically as the cytokine combination. In addition, it did not induce loss of chondrocyte zones. Treatment with inhibitors of matrix metalloproteinase (MMP) activity and nitric oxide synthesis showed that MMP activity played a part in cartilage degradation, whereas nitric oxide production did not.
  
  
  CONCLUSIONS
  IL17, together with TNFalpha, induced cartilage degradation in fetal mouse metatarsals in vitro. IL17 may, therefore, participate in the development of cartilage destruction associated with RA by enhancing the effects of TNFalpha and may provide a potential therapeutic target.
authors.affiliation: Department of Endocrinology and Metabolic Diseases, Leiden University Medical Centre, PO Box 9600, 2300 RC, Leiden, The Netherlands. R.L.van_Bezooyen@lumc.nl
authors.forename: R L
authors.initials: RL
authors.lastname: Van Bezooijen
authors.forename: L
authors.initials: L
authors.lastname: Van Der Wee-Pals
authors.forename: S E
authors.initials: SE
authors.lastname: Papapoulos
authors.forename: C W G M
authors.initials: CW
authors.lastname: Löwik
mesh_terms: D000818:Animals; D001172:Arthritis, Rheumatoid / Q000473:pathology / Q000503:physiopathology*; D002358:Cartilage, Articular / Q000187:drug effects* / Q000473:pathology; D019902:Chondrocytes / Q000187:drug effects / Q000473:pathology; D004357:Drug Synergism; D005260:Female; D020381:Interleukin-17 / Q000633:toxicity*; D020782:Matrix Metalloproteinases / Q000502:physiology; D008682:Metatarsal Bones / Q000187:drug effects* / Q000473:pathology; D051379:Mice; D009569:Nitric Oxide / Q000502:physiology; D009924:Organ Culture Techniques; D010010:Osteoclasts / Q000502:physiology; D011509:Proteoglycans / Q000187:drug effects / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000633:toxicity*
chemical_list: D020381:Interleukin-17; D011509:Proteoglycans; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D020782:Matrix Metalloproteinases