Transforming growth factor-beta regulation of collagenase, 72 kDa-progelatinase, TIMP and PAI-1 expression in rat bone cell populations and human fibroblasts.
Quiescent cultures of normal fetal rat calvarial bone cell populations (RC I and RC IV) and human fibroblasts were incubated with 1.0 ng/ml TGF-beta and the conditioned culture media were processed individually to separate collagenase and 72 kDa-progelatinase from TIMP, the tissue inhibitor of matrix metalloendoproteinases, using mini-columns of heparin- and gelatin-Sepharose. Collagenase synthesis was decreased progressively by TGF-beta in fibroblasts despite a 1.6-fold increase in secreted protein levels and a approximately 1.8-fold increase in 72 kDa-progelatinase synthesis. The human fibroblasts and the osteoblast-enriched RC IV cells showed a greater TGF-beta-induced stimulation in 72 kDa-progelatinase levels over controls compared with the RC I cells. In contrast to RC IV cells, in which TIMP mRNA levels were increased 2.9-fold by TGF-beta, the constitutive level of TIMP transcripts in the RC I cells was greater than 20-fold over that of the RC IV cells, but was not elevated by TGF-beta. TGF-beta also increased TIMP expression in fibroblasts approximately 1.7-fold and PAI-1 levels approximately 5-fold in RC IV cells, and greater than 10-fold in fibroblasts.
Overall
C M
CM
Medical Research Council Group in Periodontal Physiology, University of Toronto, Ontario, Canada.
Wrana
J L
JL
Sodek
J
J
D000818:Animals; D001857:Bone Matrix / Q000166:cytology / Q000378:metabolism; D001842:Bone and Bones / Q000166:cytology* / Q000378:metabolism; D002478:Cells, Cultured; D003238:Connective Tissue / Q000378:metabolism; D003239:Connective Tissue Cells; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism*; D018093:Gelatinases; D015870:Gene Expression / Q000187:drug effects; D006023:Glycoproteins / Q000235:genetics / Q000378:metabolism*; D008666:Metalloendopeptidases / Q000378:metabolism; D003012:Microbial Collagenase / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D010434:Pepsin A / Q000235:genetics / Q000378:metabolism*; D015849:Plasminogen Inactivators / Q000378:metabolism*; D051381:Rats; D019714:Tissue Inhibitor of Metalloproteinases; D015291:Transforming Growth Factors / Q000494:pharmacology / Q000502:physiology*
D006023:Glycoproteins; D015849:Plasminogen Inactivators; D019714:Tissue Inhibitor of Metalloproteinases; D015291:Transforming Growth Factors; D010434:Pepsin A; D018093:Gelatinases; D008666:Metalloendopeptidases; D003012:Microbial Collagenase