Inhibition of stimulated bone resorption in vitro by TIMP-1 and TIMP-2

Abstract Recombinant human TIMP-1 and TIMP-2 (tissue inhibitors of metalloproteinases) inhibited bone resorption induced by either parathyroid hormone or 1,25-dihydroxyvitamin D 3 in cultured neonatal mouse calvariae. The inhibition was reversible, dose-dependent and complete at 1 μg/ml inhibitor concentration. TIMP-2 was more potent than TIMP-1. TIMP-1 and TIMP-2 also inhibited basal bone resorption. Neither metalloproteinase inhibitor affected protein synthesis, DNA synthesis, the PTH-enhanced secretion of β-glucuronidase or the spontaneous release of lactate dehydrogenase. These results suggest that endogenous TIMPs play a central role in regulating both physiological and pathological bone resorption.