CLONING AND INITIAL CHARACTERIZATION OF MOUSE MELTRIN-BETA AND ANALYSIS OF THE EXPRESSION OF 4 METALLOPROTEASE-DISINTEGRINS IN BONE-CELLS

Here Ne report the cloning and initial biochemical characterization of the mouse metalloprotease/disintegrin/cysteine-rich (MDC) protein mel trin beta and the analysis of the mRNA expression of four MDC genes (m eltrin alpha, meltrin beta, mdc9, and mdc15) in bone cells, including osteoclasts and osteoblasts. Like most other MDC proteins, the predict ed meltrin beta protein consists of a signal sequence, prodomain, meta lloprotease domain with a predicted catalytic site, disintegrin domain , cysteine-rich region, epidermal growth factor repeat, transmembrane domain, and cytoplasmic domain with putative signaling motifs, such as potential SH3 ligand domains. Northern blot analysis indicates that m eltrin beta is widely expressed, with the highest expression in bone, heart, and lung. RNase protection studies revealed expression of all f our MDC genes analyzed here in osteoblasts, whereas only mdc9 and mdc1 5 mRNAs were detectable in osteoclast like cells generated in vitro. T reatment of primary osteoblasts with 10 nM calcitriol increased meltri n beta expression more than 3-fold, and both meltrin alpha and meltrin beta expression is apparently regulated in a differentiation associat ed manner in a mouse osteoblastic cell line, MC3T3E1. Collectively, th ese results suggest that meltrin alpha and meltrin beta may play a rol e in osteoblast differentiation and/or function but are not likely to be involved in osteoclast fusion.