INHIBITION OF STIMULATED BONE-RESORPTION INVITRO BY TIMP-1 AND TIMP-2

Recombinant human TIMP-1 and TIMP-2 (tissue inhibitors of metalloprote inases) inhibited bone resorption induced by either parathyroid hormon e or 1,25-dihydroxyvitamin D3 in cultured neonatal mouse calvariae. Th e inhibition was reversible, dose-dependent and complete at 1 mug/ml i nhibitor concentration. TIMP-2 was more potent than TIMP-1. TIMP-1 and TIMP-2 also inhibited basal bone resorption. Neither metalloproteinas e inhibitor affected protein synthesis, DNA synthesis, the PTH-enhance d secretion of beta-glucuronidase or the spontaneous release of lactat e dehydrogenase. These results suggest that endogenous TIMPs play a ce ntral role in regulating both physiological and pathological bone reso rption.