LOAD-CONTROLLED COMPRESSION OF ARTICULAR-CARTILAGE INDUCES A TRANSIENT STIMULATION OF AGGRECAN GENE-EXPRESSION

The effects of short-and long-term load-controlled compression on the levels of aggrecan mRNA have been determined. Results show that a comp ressive stress of 0.1 MPa on bovine articular cartilage explants for 1 , 4, 12, and 24 h produces a transient up-regulation of aggrecan mRNA synthesis. At 1 h, aggrecan mRNA levels in loaded explants were increa sed 3.2-fold compared to control explants, At longer times (greater th an or equal to 4 h), the levels of aggrecan mRNA returned to base-line values or stayed slightly higher. There is a dose dependence in the r esponse of the explant to increasing levels of compressive stress (0-0 .5 MPa) for 1 h. Aggrecan mRNA levels increased 2- to 3-fold at 0-0.25 MPa. At 0.5 MPa, the level of aggrecan mRNA was lower than those at 0 .1 and 0.25 MPa. This dose-dependent effect suggests a reversal of the stimulatory effects of compression on aggrecan gene expression at hig her loads. After 24 h of compression, the levels of aggrecan mRNA in e xplants subjected to any of the stress levels were not significantly d ifferent from those in control explants. The stimulatory effect of 0.1 MPa compressive stress on aggrecan mRNA levels was blocked by Rp-cAMP and U-73122, indicating the involvement of the classical signal trans duction pathways in the mechanical modulation of aggrecan gene express ion, The responses of link protein mRNA to compression paralleled thos e of aggrecan, while there was no significant change in expression of the gene for the housekeeping protein elongation factor-1 alpha. The r esults indicate that articular cartilage chondrocytes can respond to s hort-term compressive loads by transiently up-regulating expression of the aggrecan gene. The fact that long-term compression did not signif icantly alter aggrecan mRNA levels suggests that previously observed i nhibitory effects of prolonged static compression on proteoglycan synt hesis in articular cartilage may be, for the most part, mediated throu gh mechanisms other than suppression of aggrecan mRNA levels. (C) 1998 Academic Press.