Inhibition of stimulated bone resorption in vitro by TIMP-1 and TIMP-2.
Recombinant human TIMP-1 and TIMP-2 (tissue inhibitors of metalloproteinases) inhibited bone resorption induced by either parathyroid hormone or 1,25-dihydroxyvitamin D3 in cultured neonatal mouse calvariae. The inhibition was reversible, dose-dependent and complete at 1 microgram/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 beta-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.
Hill
P A
PA
Cell and Molecular Biology Department, Strangeways Research Laboratory, Cambridge UK.
Reynolds
J J
JJ
Meikle
M C
MC
D000818:Animals; D001862:Bone Resorption / Q000139:chemically induced / Q000517:prevention & control*; D002116:Calcitonin / Q000494:pharmacology; D002117:Calcitriol / Q000037:antagonists & inhibitors; D002118:Calcium / Q000032:analysis; D002478:Cells, Cultured / Q000187:drug effects; D004247:DNA / Q000096:biosynthesis; D004305:Dose-Response Relationship, Drug; D005966:Glucuronidase / Q000378:metabolism; D006023:Glycoproteins / Q000494:pharmacology* / Q000502:physiology; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D051379:Mice; D009363:Neoplasm Proteins / Q000494:pharmacology* / Q000502:physiology; D010281:Parathyroid Hormone / Q000037:antagonists & inhibitors; D011392:Proline / Q000032:analysis; D014176:Protein Biosynthesis; D011994:Recombinant Proteins / Q000494:pharmacology; D019716:Tissue Inhibitor of Metalloproteinase-2; D019714:Tissue Inhibitor of Metalloproteinases
D006023:Glycoproteins; D009363:Neoplasm Proteins; D010281:Parathyroid Hormone; D011994:Recombinant Proteins; D019714:Tissue Inhibitor of Metalloproteinases; D019716:Tissue Inhibitor of Metalloproteinase-2; D002116:Calcitonin; D004247:DNA; D011392:Proline; D007770:L-Lactate Dehydrogenase; D005966:Glucuronidase; D002117:Calcitriol; D002118:Calcium