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Parathyroid hormone‐induced resorption in fetal rat limb bones is associated with production of the metalloproteinases collagenase and gelatinase B
Author(s) -
Witty Jean P.,
Foster Shirley A.,
Stricklin George P.,
Matrisian Lynn M.,
Stern Paula H.
Publication year - 1996
Publication title -
journal of bone and mineral research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.882
H-Index - 241
eISSN - 1523-4681
pISSN - 0884-0431
DOI - 10.1002/jbmr.5650110111
Subject(s) - parathyroid hormone , interstitial collagenase , collagenase , bone resorption , endocrinology , medicine , gelatinase , resorption , calcitonin , matrix metalloproteinase , chemistry , gelatinase a , biology , calcium , enzyme , biochemistry
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 45 Ca release from the limb bones without affecting β‐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.