Transforming growth factor beta is a bifunctional regulator of replication and collagen synthesis in osteoblast-enriched cell cultures from fetal rat bone.
Transforming growth factor beta is a bifunctional regulator of replication and collagen synthesis in osteoblast-enriched cell cultures from fetal rat bone.
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DOI：
10.1016/s0021-9258(18)61587-x
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发表时间：
1987-02
期刊：
影响因子：
--
通讯作者：
M. Centrella;T. McCarthy;E. Canalis
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文献类型：
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作者：
M. Centrella;T. McCarthy;E. Canalis
转化生长因子β（TGF β）刺激胎鼠颅骨中的细胞复制，并且对分离的骨细胞的研究表明，主要的促有丝分裂反应细胞是成骨细胞谱系。TGF β对骨细胞复制的影响是双相的，并且取决于单层培养中的TGF β浓度和细胞密度。处理23小时后，融合细胞中的DNA合成逐渐增强0.15-15 ng/ml TGF β;但在亚融合细胞中，15 ng/ml小于最大值;在稀疏细胞培养物中，它是抑制性的。然而，在所有细胞密度下，15 ng/ml TGF β刺激胶原蛋白合成，当DNA合成速率下降时，这种效果更明显。此外，1 mM的羟基脲，其阻断TGF β的促有丝分裂作用达85%，仅最小程度地影响胶原蛋白合成的增加。细胞质狭缝印迹分析揭示了TGF β处理的细胞中I型胶原mRNA的量的改变，表明至少部分地在转录水平上施加控制。由于TGF β存在于由骨外植体和骨组织提取物调节的培养基中，这些结果支持TGF β是骨形成的重要和多功能的自分泌调节剂。
Transforming growth factor beta (TGF beta) stimulates cell replication in fetal rat calvariae, and studies with isolated bone cells suggest that the primary mitogenically responsive cell is of the osteoblast lineage. The effect of TGF beta on bone cell replication is biphasic and depends on both the TGF beta concentration and cell density in monolayer culture. After 23 h of treatment, DNA synthesis in confluent cells is progressively enhanced by 0.15-15 ng/ml TGF beta; but in subconfluent cells, 15 ng/ml is less than maximal; and in sparse cell cultures, it is inhibitory. At all cell densities, however, 15 ng/ml TGF beta stimulates collagen synthesis, an effect which is more pronounced when DNA synthesis rates are declining. Furthermore, 1 mM hydroxyurea, which blocks the mitogenic effect of TGF beta by 85%, only minimally influences the increase in collagen synthesis. Cytoplasmic slot blot analysis reveals alterations in the amount of type I collagen mRNA in TGF beta-treated cells, suggesting that control is exerted, at least in part, at the transcriptional level. Since TGF beta is found in culture medium conditioned by bone explants and in bone tissue extracts, these results support that TGF beta is an important and multifunctional autocrine regulator of bone formation.