MT1-MMP-deficient mice develop dwarfism, osteopenia, arthritis, and connective tissue disease due to inadequate collagen turnover

MT1-MMP is a membrane-bound matrix metalloproteinase (MT-MMP) capable of me diating pericellular proteolysis of extracellular matrix components. MT1-MM P is therefore thought to be an important molecular tool for cellular remod eling of the surrounding matrix. To establish the biological role of this m embrane proteinase we generated MT1-MMP-deficient mice by gene targeting. M T1-MMP deficiency causes craniofacial dysmorphism, arthritis, osteopenia, d warfism, and fibrosis of soft tissues due to ablation of a collagenolytic a ctivity that is essential for modeling of skeletal and extraskeletal connec tive tissues. Our findings demonstrate the pivotal function of MT1-MMP in c onnective tissue metabolism, and illustrate that modeling of the soft conne ctive tissue matrix by resident cells is essential for the development and maintenance of the hard tissues of the skeleton.