EFFECTS OF PARATHYROID-HORMONE (PTH) AND PTH-RELATED PEPTIDE ON EXPRESSIONS OF MATRIX METALLOPROTEINASE-2, METALLOPROTEINASE-3, AND METALLOPROTEINASE-9 IN GROWTH-PLATE CHONDROCYTE CULTURES

The roles of PTH and PTH-related peptide (PTH-rp) in the expression of matrix metalloproteinases (MMPs) during endochondral bone formation w ere investigated, using various cartilages obtained from young rabbits and rabbit chondrocyte cultures. Immunohistochemical, immunoblotting, zymographical, and/or Northern blot analyses showed that MMP-2 and -9 levels were much higher in the growth plate than in permanent cartila ge in vivo. In growth plate chondrocyte cultures, PTH, PTH-rp, and (Bu )(2)cAMP increased the amount of MMP-2 present in the culture medium, as revealed by zymograms and immunoblots, whereas the other tested gro wth factors or cytokines, including bone morphogenetic protein-a and i nterleukin-l, did not increase the MMP-2 level. PTH also increased the MMP-2 messenger RNA level within 24 h. In addition, PTH increased MMP -3 and -9 levels in the growth plate chondrocyte cultures. However, in articular chondrocyte cultures, PTH had little effect on the levels o f MMP-2, -3, and -9. In contrast to PTH, interleukin-1 induced MMP-3 a nd -9, but not MMP-2, in growth plate and articular chondrocytes. Thes e findings suggest that in ossifying cartilage, PTH/PTH-rp plays a piv otal role in the induction of various MMPs, including MMP-2 (which is considered to be a constitutive enzyme), and that PTH/PTH-rp is involv ed in the control of cartilage-matrix degradation during endochondral bone formation.