DIFFERENTIAL REGULATION OF MMP-13 (COLLAGENASE-3) AND MMP-3 (STROMELYSIN-1) IN MOUSE CALVARIAE

Bone resorption in mice involves the degradation of extracellular matr ix. Whereas several proteases seem to be implicated in this process, i t becomes increasingly clear that matrix metalloproteinases (MMPs), am ongst them especially MMP-13 and MMP-3, play an essential role. We hav e purified MMP-13 and MMP-3 from mouse calvariae-conditioned media by differential fractionation and analyzed their collagenolytic, caseinol ytic, gelatinolytic and proteoglycanolytic activities. It could be sho wn that in mouse calvariae-conditioned media most of the measured enzy me activities were due to MMP-13, although zymographies revealed that MMP-3, MMP-2, MMP-9 as well as TIMPs were present too. MMP-13 and MMP- 3 proteins were detected and their enzyme activities were neutralized by specific polyclonal antisera. Furthermore, it was demonstrated that in cultures of mouse calvariae the production of MMP-13 was induced b y the potent MMP-stimulator heparin and by parathyroid hormone (PTH), whereas the levels of MMP-3 remained unchanged. Although PTH-induced b one resorption was inhibited by calcitonin treatment, MMP-13 mRNA and protein expression were not significantly altered by this hormone. Tog ether with previous observations, these results indicate that PTH regu lates bone resorption through MMP-13, but not by MMP-3, and that its r eversion by calcitonin involves neither of the two enzymes. (C) 1998 E lsevier Science B.V. All rights reserved.