Growth on type I collagen promotes expression of the osteoblastic phenotype in human osteosarcoma MG-63 cells.
Using MG-63 cells as a model system capable of partial osteoblastic differentiation, we have examined the effect of growth on extracellular matrix. MG-63 cell matrix and purified type I collagen induced a morphological change characterized by long cytoplasmic processes reminiscent of those seen in osteocytes. Concurrent biochemical changes involving bone marker proteins included increased specific activity of cell-associated alkaline phosphatase and increased secretion of osteonectin (up to 2.5-fold for each protein); all changes occurred without alterations in the growth kinetics of the MG-63 cells. The increase in alkaline phosphatase activity was maximal on days 6-8 following seeding; increased osteonectin secretion was most prominent immediately following seeding; all changes decreased as cells reached confluence. Growing cells on type I collagen resulted in an increased induction of alkaline phosphatase activity by 1,25(OH)2D3 (with little change in the 1,25(OH)2D3 induction of osteonectin and osteocalcin secretion), and increased TGF-beta induction of alkaline phosphatase activity as well (both TGF-beta 1 and TGF-beta 2). Both the 1,25(OH)2D3 and TGF-beta effects appeared to be synergistic with growth on type I collagen. These studies support the hypothesis that bone extracellular matrix may play an important role in osteoblastic differentiation and phenotypic expression.
Andrianarivo
A G
AG
Department of Biochemistry, University of Vermont, Burlington 05405.
Robinson
J A
JA
Mann
K G
KG
Tracy
R P
RP
D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D001842:Bone and Bones / Q000378:metabolism; D002117:Calcitriol / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D003094:Collagen / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D010006:Osteoblasts / Q000187:drug effects / Q000473:pathology*; D015676:Osteonectin / Q000378:metabolism; D012516:Osteosarcoma / Q000235:genetics; D010641:Phenotype; D051381:Rats; D013045:Species Specificity; D013379:Substrate Specificity; D013997:Time Factors; D016212:Transforming Growth Factor beta / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D015676:Osteonectin; D016212:Transforming Growth Factor beta; D003094:Collagen; D000469:Alkaline Phosphatase; D002117:Calcitriol