Zhou H, Hammonds R G, Findlay D M, Martin T J, Ng K W
Department of Medicine, University of Melbourne, Victoria, Australia.
J Cell Physiol. 1993 Apr;155(1):112-9. doi: 10.1002/jcp.1041550115.
Transforming growth factor-beta (TGF-beta) and bone morphogenetic protein 4 (BMP 4) are both able, under certain circumstances, to induce endochondral bone formation in vivo. This study compared the effects of TGF-beta 1 and BMP 4 on the gene expression of a retinoic acid (RA) responsive rat clonal preosteoblast cell line, UMR 201, as well as the way in which these proteins interact with RA in these cells. Both similarities as well as differences between the effects and mechanism of action of TGF-beta 1 and BMP 4 were demonstrated. TGF-beta 1 (0.1 ng/ml) strongly induced matrix gla protein (MGP) mRNA and increased the steady state osteonectin (ON) mRNA level. Cotreatment with TGF-beta 1 and RA did not result in a further increase in MGP mRNA expression. In contrast, BMP 4 alone had no influence on MGP or ON mRNA expression but it significantly enhanced the RA induction of MGP mRNA. Pro-alpha 1(l) collagen mRNA was increased by TGF-beta 1 (1 ng/ml) and BMP 4 (50 ng/ml). The addition of either TGF-beta 1 or BMP 4 together with RA resulted in a further increase in pro-alpha 1 (l) collagen mRNA levels. Both RA and TGF-beta 1, but not BMP 4, increased the transcriptional rate of the pro-alpha 1 (l) collagen gene. TGF-beta 1 reduced the constitutive as well as RA-induced expression of osteopontin (OP) mRNA while BMP 4 reduced only the constitutive expression of OP mRNA. RA increased the transcriptional rate of the OP gene. Since the responses of UMR 201 cells to these structurally related factors were not identical, the results lend support to the concept that the coordinated expression of members of the TGF-beta 1 superfamily may be necessary to control the progression of specific cell types through their differentiation pathways.
转化生长因子-β（TGF-β）和骨形态发生蛋白4（BMP 4）在某些情况下均能够在体内诱导软骨内成骨。本研究比较了TGF-β1和BMP 4对维甲酸（RA）反应性大鼠克隆前成骨细胞系UMR 201基因表达的影响，以及这些蛋白质在这些细胞中与RA相互作用的方式。结果表明了TGF-β1和BMP 4在作用效果和作用机制上的异同。TGF-β1（0.1 ng/ml）强烈诱导基质γ-羧基谷氨酸蛋白（MGP）mRNA表达，并提高骨连接蛋白（ON）mRNA的稳态水平。TGF-β1与RA共同处理并未导致MGP mRNA表达进一步增加。相反，单独的BMP 4对MGP或ON mRNA表达没有影响，但它显著增强了RA对MGP mRNA的诱导作用。TGF-β1（1 ng/ml）和BMP 4（50 ng/ml）均可使I型前胶原α1（I）链（Pro-α1（I））mRNA增加。TGF-β1或BMP 4与RA一起添加导致Pro-α1（I）胶原mRNA水平进一步增加。RA和TGF-β1均可增加Pro-α1（I）胶原基因的转录速率，但BMP 4不能。TGF-β1降低骨桥蛋白（OP）mRNA的组成型表达以及RA诱导的表达，而BMP 4仅降低OP mRNA的组成型表达。RA增加OP基因的转录速率。由于UMR 201细胞对这些结构相关因子的反应并不相同，这些结果支持了这样一种观点，即TGF-β1超家族成员的协同表达可能是控制特定细胞类型通过其分化途径进展所必需的。
