A collagenolytic response to parathormone, 1,25-dihydroxycholecalciferol D3, and prostaglandin E2 in bone of osteopetrotic (mi/mi) mice.
Stimulators of bone resorption, such as PTH, 1,25-dihydroxycholecalciferol [1,25-(OH)2D3], or prostaglandin E2 (PGE2), do not cause calcium release from cultured calvaria of the genetically determined osteopetrotic microphthalmic (mi/ mi) mouse, due to a defect in the function of osteoclasts. To investigate the capacity of cells of mi/mi bone to degrade collagen, calvaria of 1- to 3-day-old normal and mi/mi littermates were labeled in vivo with [3H]proline 16 h before removal, followed by culture in resorption medium. PTH, 1,25-(OH)2D3, and PGE2 stimulated the release of 3H-labeled material into the culture medium from both normal and mi/mi calvaria. The labeled substance released was of collagenous origin, as indicated by its content of hydroxyproline and susceptibility to collagenase. PTH also stimulated the release of 3H-labeled materials from normal calvaria labeled in vivo 112 h before the mice were killed, but had little or no effect on 3H release from the mi/mi bone, indicating that only noncalcified collagen is susceptible to hormone-stimulated degradation in osteopetrotic bone. We conclude that a portion of the hormone-stimulated resorptive mechanism, namely collagenolysis, is functional in bone of mi/mi mice. This result helps to pinpoint the resorptive defect in mi/ mi bone to a failure to dissolve mineral, rather than a more general phenomenon of failure to remove both mineral and matrix.
D000818:Animals; D001842:Bone and Bones / Q000187:drug effects / Q000503:physiopathology*; D002117:Calcitriol / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D003094:Collagen / Q000378:metabolism*; D015232:Dinoprostone; D007700:Kinetics; D051379:Mice; D008817:Mice, Mutant Strains; D010022:Osteopetrosis / Q000235:genetics / Q000503:physiopathology*; D010281:Parathyroid Hormone / Q000494:pharmacology*; D011458:Prostaglandins E / Q000494:pharmacology*
D010281:Parathyroid Hormone; D011458:Prostaglandins E; D003094:Collagen; D002117:Calcitriol; D015232:Dinoprostone; D002118:Calcium