Reduced expression of BMP-3 due to mechanical loading - A link between mechanical stimuli and tissue differentiation

Mechanical signaling and BMP expression appear to be involved in controllin g the differentiation of cartilage in fracture repair, but the connection b etween mechanics and BMP signaling is not known. In this study of rats, we used a bone chamber to see how BMP gene expression was changed by a mechani cal loading regime that induces cartilage formation in this model. We com p ared the still undifferentiated tissue in loaded and un loaded chambers in the same rat regarding the expression of TGF beta -1, BMP-2, 3, 4, 5, 6, 7, CDMP-1, 2 and ALK-2 and 3 by using RT-PCR normalized against GAPDH. We fou nd expression of TGF beta -1, BMP-2 and 4 in all specimens, and BMP 5-7 and CDMPs in none, 1 week after loading started, BMP-S was strongly expressed in the un loaded control specimens in 7 of 8 animals, but detectable in onl y 1 of the contralateral loaded ones. After 2 weeks of loading, the BMP-3 e xpression pattern was less clear, but with both time groups taken together, there was still less BMP-3 expression on the loaded side in 9 rats, more i n 1 and no difference in 5 (p = 0.01). ALK-2 at 1 week was expressed in all specimens expressing BMP-3 and in none of the others. At 2 weeks, ALK-2 wa s expressed in all specimens. Thus, a loading regime, known to induce carti lage in this model, caused down-regulation of BMP-3 and ALK-2. The results are consistent with the view that BMP-3 inhibits differentiation, as recent ly described. This role appears to be linked to the ALK-2 receptor. Most im portantly, the results indicate a link between mechanical signaling and BMP expression such that me chanically-induced down-regulation of the inhibiti ng BMP-3 enabled the induction of cartilage.