Induction of rat interstitial collagenase (MMP-13) mRNA in a development-dependent manner by parathyroid hormone in osteoblastic cells

The purpose of this study was to determine whether the production of inters titial collagenase mRNA in response to parathyroid hormone (PTH) changes wi th osteoblast phenotypic development. To accomplish this, cells derived fro m fetal rat calvaria were examined. The calvarial osteoblasts, which prolif erate when placed in culture, can be made to differentiate after confluence , Studies were performed on cells while they were proliferating, at conflue nce, and during the differentiation process, The cells were treated with PT H for various times, and interstitial collagenase mRNA was quantified by RN ase protection assay. We concluded that the ability of PTH to induce inters titial collagenase mRNA in these cells increased with osteoblast phenotypic development, We also determined that the response could be mimicked by com bining the effect of 8-bromo-cAMP and 12-O-tetradecanoyl-phorbol-13-acetate , stimulate rs of the protein kinase A and protein kinase C pathways, respe ctively, both known to be activated by PTH, The binding of nuclear factors to two regions previously reported to be important for PTH induction of the gene in UMR 106-01 cells was also examined, These data indicated that the binding of nuclear factors to oligonucleotides encompassing the TRE (-51) o r the PEA3 (-80) elements changed with development of the osteoblast phenot ype. The latter was also shown to be PTH responsive.