Parathyroid hormone-induced resorption in fetal rat limb bones is associated with production of the metalloproteinases collagenase and gelatinase B.
The role of matrix metalloproteinases in parathyroid hormone (PTH)-induced bone resorption was assayed using a fetal rat limb bone culture system. Cotreatment of bones with PTH and recombinant inhibitor of metalloproteinases, TIMP-1, in vitro, inhibited the PTH-stimulated 45Ca release from the limb bones without affecting beta-glucuronidase release. TIMP-1 was fully effective when added during only the final 24 h of a 72 h culture with PTH but was ineffective when added for only the first 24 h of the 72 h culture. In contrast, calcitonin (CT) was effective when added for either the first 24 or the final 24 h of the culture. Using in situ hybridization, the mRNA for collagenase was detected in mononuclear cells of cultured bone. Treatment of the bones with PTH resulted in an increase in the number of cells producing collagenase mRNA, some of which had osteoclastic morphology, PTH also caused a dramatic induction of the mRNA for the 92-kD gelatinase B metalloproteinase in both mononuclear and osteoclastic cells. There was no detectable mRNA for the metalloproteinases stromelysin-1, stromelysin-2, or matrilysin in PTH-treated or control cultures. These results suggest that PTH-induced bone resorption is mediated, at least in part, by the induction of collagenase and gelatinase B mRNA in bone cells.
Witty
J P
JP
Department of Cell Biology, Vanderbilt University, Nashville, Tennessee, USA.
Foster
S A
SA
Stricklin
G P
GP
Matrisian
L M
LM
Stern
P H
PH
D000818:Animals; D001862:Bone Resorption / Q000139:chemically induced* / Q000201:enzymology* / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D017364:Collagenases / Q000096:biosynthesis* / Q000235:genetics; D018076:DNA, Complementary; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006023:Glycoproteins / Q000494:pharmacology; D017403:In Situ Hybridization; D020780:Matrix Metalloproteinase 9; D061965:Matrix Metalloproteinase Inhibitors; D009924:Organ Culture Techniques; D010281:Parathyroid Hormone / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D019714:Tissue Inhibitor of Metalloproteinases
D018076:DNA, Complementary; D004791:Enzyme Inhibitors; D006023:Glycoproteins; D061965:Matrix Metalloproteinase Inhibitors; D010281:Parathyroid Hormone; D012333:RNA, Messenger; D019714:Tissue Inhibitor of Metalloproteinases; D017364:Collagenases; D020780:Matrix Metalloproteinase 9; D002118:Calcium