title: Responsiveness of articular cartilage from normal and inflamed mouse knee joints to various growth factors.
abstract: OBJECTIVE
  Disturbed anabolic signalling might contribute to the decreased chondrocyte proteoglycan (PG) synthesis during joint inflammation. Articular cartilage obtained from mouse knee joints with experimentally-induced arthritis exhibits a state of nonresponsiveness towards stimulation of chondrocyte PG synthesis by insulin-like growth factor-1 (IGF-1). Investigations were carried out on the role of other growth factors apart from IGF-1 on regulation of chondrocyte PG synthesis under pathological conditions, that is, during repair after IL-1 exposure as well as during early and later arthritis.
  
  
  METHODS
  Mouse patellae were obtained from normal knee joints and joints injected with IL-1 or zymosan. The patellae were cultured with basic fibroblast growth factor [bFGF], platelet-derived growth factor [PDGF], epidermal growth factor [EGF] or transforming growth factor beta [TGF beta] for 24 hours in the presence or absence of IGF-1. Chondrocyte PG synthesis was measured by 35S-sulphate incorporation.
  
  
  RESULTS
  In normal cartilage none of the tested growth factors elicited stimulatory effects on the chondrocyte PG synthesis as caused by IGF-1. EGF and TGF beta even caused significant inhibition of chondrocyte PG synthesis. Combination of bFGF or PDGF with IGF-1 exerted significant additional stimulation of the 35S-sulphate incorporation. IL-1 exposed cartilage displayed reactivity to IGF-1 as well as to the other growth factors similar to control cartilage. Cartilage obtained from joints with experimentally-induced arthritis exhibited a state of nonresponsiveness towards all individually tested growth factors as well as growth factor combinations.
  
  
  CONCLUSIONS
  Arthritis causes nonresponsiveness to stimulation of chondrocyte PG synthesis by the tested growth factors, which might be caused by a general receptor function defect.
authors.affiliation: Department of Rheumatology, University Hospital Nijmegen, The Netherlands.
authors.forename: P J
authors.initials: PJ
authors.lastname: Verschure
authors.forename: L A
authors.initials: LA
authors.lastname: Joosten
authors.forename: P M
authors.initials: PM
authors.lastname: van der Kraan
authors.forename: W B
authors.initials: WB
authors.lastname: Van den Berg
mesh_terms: D000818:Animals; D001169:Arthritis, Experimental / Q000378:metabolism*; D002358:Cartilage, Articular / Q000187:drug effects* / Q000378:metabolism; D004815:Epidermal Growth Factor / Q000494:pharmacology; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology; D006133:Growth Substances / Q000494:pharmacology*; D066298:In Vitro Techniques; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D010329:Patella; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D011453:Prostaglandins / Q000096:biosynthesis*; D016212:Transforming Growth Factor beta / Q000494:pharmacology
chemical_list: D006133:Growth Substances; D010982:Platelet-Derived Growth Factor; D011453:Prostaglandins; D016212:Transforming Growth Factor beta; D016222:Fibroblast Growth Factor 2; D004815:Epidermal Growth Factor; D007334:Insulin-Like Growth Factor I