The effect of dynamic compression on the response of articular cartilage to insulin-like growth factor-I.
Articular cartilage is routinely subjected to mechanical forces and to cell-regulatory molecules. Previous studies have shown that mechanical stimuli can influence articular chondrocyte metabolic activity, and biochemical studies have shown that growth factors and cytokines control many of the same cell functions. Little is known, however, of the relationships or interplay, if any, between these two key components of the articular environment. This study investigated the comparative and interactive effects of low amplitude, sinusoidal, dynamic compression and insulin-like growth factor-I (IGF-I), a polypeptide in synovial fluid that is anabolic for cartilage. In bovine patellofemoral cartilage explants, IGF-I increased protein and proteoglycan synthesis 90% and 120%, respectively while dynamic compression increased protein and proteoglycan synthesis 40% and 90%, respectively. Stimulation by IGF-I was significantly greater than by dynamic compression for both protein and proteoglycan synthesis. When applied together, the two stimuli enhanced protein and proteoglycan synthesis by 180% and 290%, respectively, a degree greater than that achieved by either stimulus alone. IGF-I augmented protein synthesis with a time constant of 12.2 h. Dynamic compression increased protein synthesis with a time constant of 2.9 h, a rate significantly faster than that of IGF-I, suggesting that these signals act via distinct cell activation pathways. When used together, dynamic compression and IGF-I acted with a time constant of 5.6 h. Thus, dynamic compression accelerated the biosynthetic response to IGF-I and increased transport of IGF-I into the articular cartilage matrix, suggesting that, in addition to independently stimulating articular chondrocytes, cyclic compression may improve the access of soluble growth factors to these relatively isolated cells.
Bonassar
L J
LJ
Orthopaedic Research Laboratories, Massachusetts General Hospital, Harvard Medical School, Boston 02114, USA.
Grodzinsky
A J
AJ
Frank
E H
EH
Davila
S G
SG
Bhaktav
N R
NR
Trippel
S B
SB
D000818:Animals; D001692:Biological Transport; D002358:Cartilage, Articular / Q000187:drug effects* / Q000378:metabolism; D002417:Cattle; D004305:Dose-Response Relationship, Drug; D007334:Insulin-Like Growth Factor I / Q000378:metabolism / Q000494:pharmacology*; D011312:Pressure; D011392:Proline / Q000378:metabolism
D007334:Insulin-Like Growth Factor I; D011392:Proline