title: Insulin-like growth factor stimulation of articular chondrocyte proteoglycan synthesis. Availability and responses at different ages.
abstract: It was found that recovery of articular chondrocyte proteoglycan (PG) synthesis was retarded in old mice after in vivo exposure to both IL-1 or hydrogen peroxide. We examined whether this could be related to diminished serum levels of insulin-like growth factor 1 (IGF-1), the main anabolic factor, or to changes in cartilage IGF responsiveness with age. A small decline of IGF-1 concentration was observed in serum of old mice, but the level still appeared to be supra-optimal to maintain normal cartilage PG synthesis over a culture period of 1 to 3 days. Moreover, PG synthesis was at least equally stimulated in patellar cartilage from 18-month-old mice compared to 3-month-old mice over a wide range of IGF-1 concentrations, and similar findings were obtained after stimulation with serum. In addition, we studied the capacity of IGF-1 or serum to induce recovery of PG synthesis in vitro after IL-1 exposure in vivo. In a 3-day culture period normal cartilage PG synthesis was stimulated to the same extent with serum or IGF-1, but recovery from IL-1 mediated suppression of PG synthesis was more pronounced with serum. This latter capacity was similar for serum of mice aged 3 or 18 months and was noted for both young and old cartilage. Our data show that retarded recovery of chondrocyte PG synthesis in old mice cannot be explained by age-related changes in IGF-1 availability and cartilage responses to IGF. They also indicate that serum factors other than IGF-1 are important for recovery, either alone or in combination with IGF-1.
authors.affiliation: Department of Rheumatology, University Hospital St. Radboud, Nijmegen, The Netherlands.
authors.forename: H M
authors.initials: HM
authors.lastname: van Beuningen
authors.forename: O J
authors.initials: OJ
authors.lastname: Arntz
authors.forename: W B
authors.initials: WB
authors.lastname: van den Berg
mesh_terms: D000375:Aging / Q000378:metabolism*; D000818:Animals; D001682:Biological Availability; D002358:Cartilage, Articular / Q000166:cytology / Q000378:metabolism*; D002417:Cattle; D005260:Female; D006861:Hydrogen Peroxide / Q000494:pharmacology; D007270:Injections, Intra-Articular; D007334:Insulin-Like Growth Factor I / Q000032:analysis / Q000494:pharmacology*; D007375:Interleukin-1 / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D011509:Proteoglycans / Q000096:biosynthesis* / Q000493:pharmacokinetics; D011994:Recombinant Proteins
chemical_list: D007375:Interleukin-1; D011509:Proteoglycans; D011994:Recombinant Proteins; D007334:Insulin-Like Growth Factor I; D006861:Hydrogen Peroxide