Leukemia inhibitory factor and oncostatin M stimulate collagenase-3 expression in osteoblasts

Leukemia inhibitory factor (LIF) and oncostatin M (OSM) have multiple effec ts on skeletal remodeling. Although these cytokines modestly regulate colla gen synthesis in osteoblasts, their effects on collagenase expression and c ollagen degradation are not known. We tested whether LIF and OSM regulate t he expression of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) in osteoblast-enriched cells isolated from fetal rat calvariae. LIF and OSM increased collagenase-3 (MMP-13) mRNA and immun oreactive protein levels in a time- and dose-dependent manner. LIF and OSM enhanced the rate of transcription of the collagenase gene and stabilized c ollagenase mRNA in transcriptionally arrested cells. LIF and OSM failed to regulate the expression of gelatinase A (MMP-2) and B (MMP-9). LIF and OSM modestly stimulated the expression of TIMP-1 but did not alter the expressi on of TIMP-2 and -3. In conclusion, LIF and OSM stimulate collagenase-3 and TIMP-1 expression in osteoblasts, and these effects may be involved in med iating the bone remodeling actions of these cytokines.