title: Mechanical and physicochemical regulation of the action of insulin-like growth factor-I on articular cartilage.
abstract: The development and maintenance of healthy joints is a complex process involving many physical and biological stimuli. This study investigates the interaction between insulin-like growth factor-I (IGF-I) and static mechanical compression in the regulation of articular cartilage metabolism. Bovine cartilage explants were treated with concentrations of IGF-I from 0 to 300 ng/ml in the presence or absence of 0-50% static compression, and the transient and steady-state incorporation of [(3)H]proline and [(35)S]sulfate into matrix components were measured. In parallel studies, cartilage explants were treated with 0-300 ng/ml IGF-I at media pH ranging from 6.4 to 7.2 and the steady-state incorporation of [(3)H]proline and [(35)S]sulfate was measured. The effect of 50% static compression on IGF-I transport was determined by measuring the uptake of (125)I-labeled IGF-I into cartilage explants. Static compression decreased both [(3)H]proline and [(35)S]sulfate incorporation in a dose-dependent manner in the presence or absence of IGF-I. IGF-I increased [(3)H]proline and [(35)S]sulfate incorporation in a dose-dependent manner in the presence or absence of compression, but the anabolic effect of the growth factor was lessened when the tissue was compressed by 50%. The response of cartilage explants to IGF-I was similarly lessened in unstrained tissue cultured in media at pH 6.4, a condition which results in a similar intratissue pH to that when cartilage is compressed by 50%. The characteristic time constant (tau) for IGF-I stimulation of cartilage explants was approximately 24 h, while tau for inhibition of biosynthesis by static compression was approximately 2 h. Samples which were both compressed and treated with IGF-I demonstrated an initial decrease in biosynthetic activity at 2 h, followed by an increase at 24 h. Static compression did not alter tau for (125)I-labeled IGF-I transport into cartilage but decreased the concentration of (125)I-labeled IGF-I in the tissue at equilibrium.
authors.affiliation: Orthopaedic Research Laboratories, Massachusetts General Hospital, Boston, Massachusetts, 02114, USA. Lawrence.Bonassar@umassmed.edu
authors.forename: L J
authors.initials: LJ
authors.lastname: Bonassar
authors.forename: A J
authors.initials: AJ
authors.lastname: Grodzinsky
authors.forename: A
authors.initials: A
authors.lastname: Srinivasan
authors.forename: S G
authors.initials: SG
authors.lastname: Davila
authors.forename: S B
authors.initials: SB
authors.lastname: Trippel
mesh_terms: D000818:Animals; D001692:Biological Transport; D002358:Cartilage, Articular / Q000187:drug effects*; D002417:Cattle; D005109:Extracellular Matrix / Q000187:drug effects; D006023:Glycoproteins / Q000096:biosynthesis; D006863:Hydrogen-Ion Concentration; D007334:Insulin-Like Growth Factor I / Q000378:metabolism / Q000494:pharmacology*; D007457:Iodine Radioisotopes; D007700:Kinetics; D009924:Organ Culture Techniques; D011392:Proline / Q000378:metabolism; D013314:Stress, Mechanical; D013431:Sulfates / Q000378:metabolism; D013997:Time Factors
chemical_list: D006023:Glycoproteins; D007457:Iodine Radioisotopes; D013431:Sulfates; D007334:Insulin-Like Growth Factor I; D011392:Proline