Degradation of type I collagen films by mouse osteoblasts is stimulated by 1,25 dihydroxyvitamin D3 and inhibited by human recombinant TIMP (tissue inhibitor of metalloproteinases).
Mouse calvarial osteoblasts grown on native type I collagen films degrade collagen in response to 1,25 (OH) 2vitD3. Collagen degradation is accompanied by increased latent collagenase and gelatinase secretion and by a reduction in free TIMP. Exogenous human recombinant TIMP abolished 1,25 (OH) 2vitD3 stimulated collagen degradation and inhibited background collagenolysis. No active metalloproteinases were detectable in the culture medium suggesting sequestration of active enzyme at the site of action or inhibition by residual TIMP. Chondrocytes could not mimic osteoblasts in this system.
Thomson
B M
BM
Cell Physiology, Strangeways Research Laboratory, Worts Causeway, Cambridge.
Atkinson
S J
SJ
Reynolds
J J
JJ
Meikle
M C
MC
D000818:Animals; D000831:Animals, Newborn; D002117:Calcitriol / Q000494:pharmacology*; D002356:Cartilage / Q000187:drug effects / Q000378:metabolism; D002478:Cells, Cultured; D003094:Collagen / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D018093:Gelatinases; D006801:Humans; D007700:Kinetics; D051379:Mice; D003012:Microbial Collagenase / Q000378:metabolism*; D010006:Osteoblasts / Q000187:drug effects / Q000378:metabolism*; D010434:Pepsin A / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology*; D019714:Tissue Inhibitor of Metalloproteinases
D004791:Enzyme Inhibitors; D011994:Recombinant Proteins; D019714:Tissue Inhibitor of Metalloproteinases; D003094:Collagen; D010434:Pepsin A; D018093:Gelatinases; D003012:Microbial Collagenase; D002117:Calcitriol