Chen T L, Bates R L
Department of Developmental Biology, Genentech, Inc., South San Francisco, California.
J Bone Miner Res. 1993 Apr;8(4):423-34. doi: 10.1002/jbmr.5650080406.
TGF-beta 1 increases cell proliferation and collagen synthesis in osteoblast-like cells and bone organ cultures. However, the effects of TGF-beta 1 on bone resorption remain contradictory. Therefore, the exact role that this growth factor plays in the process of bone remodeling is still not clear. We studied the effects of recombinant human TGF-beta 1 (rhTGF-beta 1) on bone formation and resorption in a mineralizing bone organ culture system. Parietal bones from 20-day-old fetal rat calvariae were cultured up to 7 days in serum-free BGJb medium. They responded to a 1 day pulse or continuous treatment of rhTGF-beta 1 with dose-dependent increases in dry weight, [3H]thymidine ([3H]TdR) incorporation, and collagen synthesis. In contrast, rhTGF-beta 1 reduced the calcium content of the bones. This is not due to increased bone resorption but rather to failure of calcium deposition. The following responses occurred at 1 nM rhTGF-beta 1. Dry weight was increased 25-50% after 6 days in culture. DNA synthesis was increased to a maximum at day 1, reaching twofold of the control level. Adding hydroxyurea at day 0 reduced [3H]TdR incorporation in rhTGF-beta 1 treated bones to 20% of the control and indomethacin abrogated the increase in [3H]TdR stimulated by rhTGF-beta 1 to the control level. Both treatments completely blocked the increase in dry weight induced by rhTGF-beta 1 at day 6. rhTGF-beta 1 stimulated collagen synthesis to reach its maximum at day 2, with a twofold increase in [3H]proline incorporation. Basal alkaline phosphatase activity fell continuously in culture, reaching 35% of day 0 level at day 6. Enzyme activity was not altered by rhTGF-beta 1. Morphologic observations by light and electron microscopy confirmed these findings. In summary, rhTGF-beta 1 altered bone remodeling by increasing organic components and decreasing calcification in a mineralizing bone organ culture system.
转化生长因子β1（TGF-β1）可促进成骨样细胞和骨器官培养物中的细胞增殖及胶原蛋白合成。然而，TGF-β1对骨吸收的影响仍存在矛盾之处。因此，这种生长因子在骨重塑过程中的确切作用仍不明确。我们在矿化骨器官培养系统中研究了重组人TGF-β1（rhTGF-β1）对骨形成和吸收的影响。将20日龄胎鼠颅骨的顶骨在无血清BGJb培养基中培养7天。它们对rhTGF-β1进行1天脉冲或连续处理后，干重、[3H]胸腺嘧啶核苷（[3H]TdR）掺入量和胶原蛋白合成呈剂量依赖性增加。相反，rhTGF-β1降低了骨骼的钙含量。这并非由于骨吸收增加，而是钙沉积失败所致。在1 nM rhTGF-β1时出现以下反应。培养6天后干重增加25 - 50%。DNA合成在第1天增加至最大值，达到对照水平的两倍。在第0天添加羟基脲可将rhTGF-β1处理的骨骼中[3H]TdR掺入量降至对照的20%，吲哚美辛可将rhTGF-β1刺激的[3H]TdR增加恢复至对照水平。两种处理均完全阻断了rhTGF-β1在第6天诱导的干重增加。rhTGF-β1刺激胶原蛋白合成在第2天达到最大值，[3H]脯氨酸掺入量增加两倍。基础碱性磷酸酶活性在培养过程中持续下降，在第6天降至第0天水平的35%。rhTGF-β不改变酶活性。光镜和电镜下的形态学观察证实了这些发现。总之，在矿化骨器官培养系统中，rhTGF-β1通过增加有机成分和减少钙化改变了骨重塑。
