Collagenase Cleavage of Type I Collagen Is Essential for Both Basal and Parathyroid Hormone (PTH)/PTH-Related Peptide Receptor-Induced Osteoclast Activation and Has Differential Effects on Discrete Bone Compartments

Expression of a constitutively active PTH/PTHrP receptor in cells of osteoblast lineage in vivo (CL2+) causes increases in trabecular bone volume and trabecular bone formation and, conversely, a decrease in the periosteal mineral apposition rate. Collagenase-3 (matrix metalloprotease-13) is a downstream target of PTH action. To investigate the relevance of collagenase cleavage of type I collagen for the CL2+ bone phenotype, we bred CL2+ animals with mice carrying a mutated col1α1 gene that encodes a protein resistant to digestion by collagenase-3 and other collagenases (rr). Adult tibias and parietal bones from 4-wk-old double-mutant animals (CL2+/rr) and from control littermates were analyzed. Trabecular bone volume was higher in CL2+/rr than in CL2+ mice. This increase occurred despite a modest reduction in bone formation rate, which was, however, still significantly higher that in wild-type littermates, and therefore must reflect decreased bone resorption in rr mice. Osteoclast number was increased in ...