Regulation of collagenase-3 by bone morphogenetic protein-2 in bone cell cultures.
Bone morphogenetic protein-2 (BMP-2), a member of the transforming growth factor superfamily of peptides, induces ectopic bone formation in vivo. The actions of BMP-2 on osteoblastic cells include stimulation of collagen synthesis, but the role of BMP-2 on collagen degradation is not known. We examined whether BMP-2 affects the expression of collagenase-3, an enzyme that degrades type I collagen at neutral pH, and that of tissue inhibitors of matrix metalloproteinases (TIMPs) in primary osteoblast-enriched cells from 22-day-old fetal rat calvariae. BMP-2 suppressed collagenase messenger RNA (mRNA) and immunoreactive protein levels. BMP-2 did not affect collagenase mRNA stability, but it reduced collagenase heterogeneous nuclear RNA levels and decreased the rate of transcription of the collagenase gene. BMP-2 also stimulated TIMP 1 and TIMP 3 mRNA levels, but failed to alter TIMP 2 expression. In conclusion, our studies indicate that BMP-2 suppresses collagenase-3 gene transcription and stimulates TIMP 1 and TIMP 3 expression in osteoblasts. The regulation of collagenase and TIMPs by BMP-2 in osteoblasts may play a role in osteoinduction.
Varghese
S
S
Department of Research, Saint Francis Hospital and Medical Center, Hartford, Connecticut 06105, USA.
Canalis
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E
D000818:Animals; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins / Q000502:physiology*; D002478:Cells, Cultured; D017364:Collagenases / Q000235:genetics / Q000378:metabolism*; D004792:Enzyme Precursors / Q000378:metabolism; D006023:Glycoproteins / Q000378:metabolism; D053509:Matrix Metalloproteinase 13; D011480:Protease Inhibitors / Q000378:metabolism; D011506:Proteins / Q000378:metabolism; D012333:RNA, Messenger / Q000037:antagonists & inhibitors; D051381:Rats / Q000196:embryology; D012886:Skull / Q000166:cytology / Q000196:embryology / Q000201:enzymology*; D019716:Tissue Inhibitor of Metalloproteinase-2; D019717:Tissue Inhibitor of Metalloproteinase-3; D019714:Tissue Inhibitor of Metalloproteinases; D014158:Transcription, Genetic; D016212:Transforming Growth Factor beta
C525720:Bmp2 protein, rat; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins; D004792:Enzyme Precursors; D006023:Glycoproteins; D011480:Protease Inhibitors; D011506:Proteins; D012333:RNA, Messenger; D019717:Tissue Inhibitor of Metalloproteinase-3; D019714:Tissue Inhibitor of Metalloproteinases; D016212:Transforming Growth Factor beta; D019716:Tissue Inhibitor of Metalloproteinase-2; D017364:Collagenases; D053509:Matrix Metalloproteinase 13; C507083:Mmp13 protein, rat; C022440:procollagenase