REGULATION OF INTERSTITIAL COLLAGENASE EXPRESSION AND COLLAGEN DEGRADATION BY RETINOIC ACID IN BONE-CELLS

In osteoblasts, retinoic acid (RA) modulates the synthesis of various proteins, including collagen. However, little is known about the effec ts of RA on the regulation of interstitial collagenase synthesis and c ollagen degradation. After treatment of primary osteoblast-enriched (O b cells from fetal rat calvariae with 100 nM all-trans-RA (tRA), colla genase mRNA levels, as determined by Northern blotting, did not change after 2 h, increased by 13- to 18-fold after 6 h, and remained elevat ed until 48 h. Exposure of Ob cells to 10 nM to 1 mu M tRA, 13-cis-RA, and 9-cis-RA induced collagenase mRNA in a dose-dependent manner. Col lagenase mRNA induction by RA was blocked by cycloheximide. RA increas ed the stability of collagenase mRNA in Ob cells, suggesting posttrans criptional regulation. Exposure of Ob cells to RA induced immunoreacti ve procollagenase in medium, as determined by enzyme-linked immunosorb ent assay and Western blotting. RA action on collagen degradation was examined in [H-3]proline-pulsed intact calvariae chased with and witho ut tRA for 72 h, The release of [H-3]hydroxyproline into culture mediu m was increased by 64% in the presence of 10 nM to 1 mu M tRA. In conc lusion, RA increases collagenase synthesis and collagen degradation in bone and is likely to play an important role in bone remodeling.