Transforming growth factor-beta regulation of collagenase, 72 kDa-progelatinase, TIMP and PAI-1 expression in rat bone cell populations and human fibroblasts

Connect Tissue Res. 1989;20(1-4):289-94. doi: 10.3109/03008208909023899.


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.

MeSH terms

  • Animals
  • Bone Matrix / cytology
  • Bone Matrix / metabolism
  • Bone and Bones / cytology*
  • Bone and Bones / metabolism
  • Cells, Cultured
  • Connective Tissue / metabolism
  • Connective Tissue Cells
  • Fibroblasts / cytology
  • Fibroblasts / metabolism*
  • Gelatinases
  • Gene Expression / drug effects
  • Glycoproteins / genetics
  • Glycoproteins / metabolism*
  • Metalloendopeptidases / metabolism
  • Microbial Collagenase / antagonists & inhibitors
  • Microbial Collagenase / genetics
  • Microbial Collagenase / metabolism*
  • Pepsin A / genetics
  • Pepsin A / metabolism*
  • Plasminogen Inactivators / metabolism*
  • Rats
  • Tissue Inhibitor of Metalloproteinases
  • Transforming Growth Factors / pharmacology
  • Transforming Growth Factors / physiology*


  • Glycoproteins
  • Plasminogen Inactivators
  • Tissue Inhibitor of Metalloproteinases
  • Transforming Growth Factors
  • Pepsin A
  • Gelatinases
  • Metalloendopeptidases
  • Microbial Collagenase