Tanaka H, Liang C T
Gerontology Research Center, National Institute on Aging, National Institutes of Health, Baltimore, Maryland 21224, USA.
J Cell Physiol. 1995 Aug;164(2):367-75. doi: 10.1002/jcp.1041640217.
The effects of platelet-derived growth factor (PDGF) on DNA synthesis and mRNA expression of osteoblast markers in marrow stromal cells derived from adult (6 months) and old (24 months) rats were examined. Treatment of stromal cells from adult rats with dexamethasone induced the appearance of osteoblast-like cells. PDGF partially also inhibited the differentiation of stromal cells induced by dexamethasone. In cultures of serum-starved stromal cells, PDGF stimulated [3H]-thymidine incorporation into DNA in a dose-dependent manner with a maximum stimulation of 15-fold at 500 ng/ml. By comparison, insulin-like growth factor (IGF-I) has a small effect on [3H]-thymidine incorporation. The effect of PDGF and IGF-I on DNA synthesis was additive. Treatment of the confluent stromal cells from adult rats with PDGF increased the mRNA level of osteopontin fourfold without any significant effect on alkaline phosphatase and type I collagen mRNAs. In contrast, dexamethasone stimulated the mRNA expression of alkaline phosphatase, type I collagen, and osteopontin 2.1-, 2.3-, and 14-fold, respectively. Addition of PDGF to dexamethasone-treated cells failed to induce any further increase in osteopontin expression whereas the expression of alkaline phosphatase and type I collagen was partially reduced. The expression of osteocalcin mRNA was negligible in stromal cells but stimulated several fold by dexamethasone and 1,25(OH)2D3. PDGF inhibited drastically the elevation of osteocalcin mRNA. In contrast, IGF-I stimulated type I collagen expression 100% without any appreciable effect on the expression of osteopontin and alkaline phosphatase. The stimulatory effect of PDGF on osteopontin expression was augmented by IGF-I. Furthermore, PDGF attenuated the stimulatory effect of IGF-I on type I collagen expression. The responses of cultured cells from old rats to growth factors were also examined. PDGF or PDGF plus IGF-I increased [3H]-thymidine incorporation in stromal cells from old rats but to a lesser extent. However, PDGF was equally effective in stimulating osteopontin expression in cells from both adult and old rats. We concluded that PDGF is a potent mitogen but that the response of stromal cells from old rats is impaired. In addition, PDGF stimulates osteopontin expression in stromal cells and this effect is not age dependent.
研究了血小板衍生生长因子（PDGF）对成年（6个月）和老年（24个月）大鼠骨髓基质细胞中DNA合成及成骨细胞标志物mRNA表达的影响。用地塞米松处理成年大鼠的基质细胞可诱导成骨样细胞出现。PDGF也部分抑制了地塞米松诱导的基质细胞分化。在血清饥饿的基质细胞培养物中，PDGF以剂量依赖方式刺激[3H] - 胸腺嘧啶核苷掺入DNA，在500 ng/ml时最大刺激倍数为15倍。相比之下，胰岛素样生长因子（IGF - I）对[3H] - 胸腺嘧啶核苷掺入的影响较小。PDGF和IGF - I对DNA合成的作用是相加的。用PDGF处理成年大鼠汇合的基质细胞可使骨桥蛋白的mRNA水平增加四倍，而对碱性磷酸酶和I型胶原mRNA无明显影响。相反，地塞米松分别刺激碱性磷酸酶、I型胶原和骨桥蛋白的mRNA表达2.1倍、2.3倍和14倍。将PDGF添加到用地塞米松处理的细胞中未能诱导骨桥蛋白表达进一步增加，而碱性磷酸酶和I型胶原的表达则部分降低。骨钙素mRNA在基质细胞中的表达可忽略不计，但用地塞米松和1,25(OH)2D3刺激后可增加数倍。PDGF显著抑制骨钙素mRNA的升高。相反，IGF - I刺激I型胶原表达100%，而对骨桥蛋白和碱性磷酸酶的表达无明显影响。IGF - I增强了PDGF对骨桥蛋白表达的刺激作用。此外，PDGF减弱了IGF - I对I型胶原表达的刺激作用。还研究了老年大鼠培养细胞对生长因子的反应。PDGF或PDGF加IGF - I可增加老年大鼠基质细胞中[3H] - 胸腺嘧啶核苷的掺入，但程度较小。然而，PDGF在刺激成年和老年大鼠细胞中的骨桥蛋白表达方面同样有效。我们得出结论，PDGF是一种有效的促有丝分裂原，但老年大鼠基质细胞的反应受损。此外，PDGF刺激基质细胞中骨桥蛋白的表达，且这种作用不依赖年龄。
