Effects of transforming growth factor beta 1 and L-ascorbate on synthesis and distribution of proteoglycans in murine osteoblast-like cells.
Proteoglycans synthesized by osteoblasts are incorporated into bone matrix and thought to play a role in bone metabolism. Transforming growth factor (TGF) beta affects the synthesis of matrix proteins, including proteoglycans, in various stromal cells, and proteoglycans, especially decorin, are associated with matrix collagen. In the present study, the effects of TGF-beta 1 and L-ascorbate, a factor essential for collagen synthesis, on the synthesis and distribution of proteoglycans were examined using murine osteoblast-like MC3T3-E1 cells. TGF-beta 1 stimulated the synthesis of proteoglycans in MC3T3-E1 cells. Among various proteoglycans, the synthesis of decorin was preferentially enhanced by TGF-beta 1, and the effect was more pronounced on secreted decorin compared to that associated with the cell/matrix layer. TGF-beta 1 also stimulated the initiation and elongation of the dermatan sulfate glycosaminoglycan chain, resulting in a larger molecular size of decorin. TGF-beta 1 influenced the synthesis of a heparan sulfate proteoglycan only slightly. L-ascorbate had no effect on the synthesis of proteoglycans, but increased those associated with the cell/matrix layer. Furthermore, when L-ascorbate was added to the culture along with TGF-beta 1, the percentage of proteoglycans associated with the cell/matrix layer increased from 25.8 +/- 1.0 to 41.0 +/- 0.5%. These data demonstrate that TGF-beta 1 markedly stimulates the synthesis of proteoglycans, especially decorin, mainly as a secreting form, that the accumulation of decorin into matrix is enhanced by L-ascorbate, and that the effects of TGF-beta 1 and L-ascorbate are additive.(ABSTRACT TRUNCATED AT 250 WORDS)
Takeuchi
Y
Y
Fourth Department of Internal Medicine, University of Tokyo School of Medicine, Japan.
Matsumoto
T
T
Ogata
E
E
Shishiba
Y
Y
D016475:3T3 Cells / Q000187:drug effects; D000818:Animals; D001205:Ascorbic Acid / Q000494:pharmacology*; D002460:Cell Line; D011508:Chondroitin Sulfate Proteoglycans / Q000096:biosynthesis*; D058575:Decorin; D003871:Dermatan Sulfate / Q000096:biosynthesis*; D004357:Drug Synergism; D004591:Electrophoresis, Polyacrylamide Gel; D016326:Extracellular Matrix Proteins; D006025:Glycosaminoglycans / Q000096:biosynthesis; D019812:Heparan Sulfate Proteoglycans; D006497:Heparan Sulfate / Q000096:biosynthesis*; D051379:Mice; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D011509:Proteoglycans / Q000096:biosynthesis*; D013237:Stereoisomerism; D016212:Transforming Growth Factor beta / Q000494:pharmacology*
D001205:Ascorbic Acid; D011508:Chondroitin Sulfate Proteoglycans; D058575:Decorin; D003871:Dermatan Sulfate; D016326:Extracellular Matrix Proteins; D006025:Glycosaminoglycans; D019812:Heparan Sulfate Proteoglycans; D006497:Heparan Sulfate; D011509:Proteoglycans; D016212:Transforming Growth Factor beta; C546879:Dcn protein, mouse; C032649:dermatan sulfate proteoglycan