Recombinant TGF-beta1 stimulates bone marrow osteoprogenitor cell activity and bone matrix synthesis in osteopenic, old male mice.
Recombinant TGF-beta1 stimulates bone marrow osteoprogenitor cell activity and bone matrix synthesis in osteopenic, old male mice.
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发表时间：
1999
影响因子：
4
通讯作者：
D. Gazit;Y. Zilberman;G. Turgeman;S. Zhou;A. Kahn
中科院分区：
文献类型：
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作者：
D. Gazit;Y. Zilberman;G. Turgeman;S. Zhou;A. Kahn
我们以前假设，在老年雄性BALB/c小鼠骨骼中观察到的骨质减少变化是由于骨TGF-β的可用性和/或合成减少，这导致更少、更少的成骨骨髓骨祖细胞（CFU-f; OPCs）和更低的骨形成水平。除此之外，这一假设将预测，将外源性TGF-β引入老年小鼠（生长因子替代）应刺激骨髓CFU-f并增加骨形成。在目前的研究中，我们已经验证了这一预测，并间接的假设，通过注射人重组TGF-β 1，i. p.，进入年轻成年小鼠（4个月）和老年小鼠（24个月）。然后通过测量骨小梁体积、骨形成、骨折愈合以及骨髓CFU-f/OPCs的数量、增殖、凋亡和碱性磷酸酶活性来评估生长因子对骨骼的影响。我们的数据显示，将0.5或5.0 μ g/天的TGF-β 1导入老年小鼠20天：1）增加骨小梁体积、骨形成和矿物质沉积率，2）增强骨折愈合，3）增加CFU-f集落的数量和大小，4）增加原代骨髓培养物中CFU-f的增殖并减少其凋亡。重要的是，注射生长因子的这些刺激作用显然是年龄特异性的，即，它们要么在幼年动物中看不到，要么即使看到，也在低得多的水平上发现。虽然这些观察结果并不排除老年小鼠骨质减少的其他可能机制，但它们为以下假设提供了进一步的支持：随着年龄的增长，TGF-β合成或可用性减少导致骨髓骨祖细胞库和骨形成减少。研究结果还表明，后者的变化可以逆转，至少是暂时的，通过引入外源性TGF-β 1。
We have previously hypothesized that the osteopenic changes seen in the skeletons of old male BALB/c mice are due to reductions in the availability and/or synthesis of bone TGF-beta which results in fewer, less osteogenic marrow osteoprogenitor cells (CFU-f; OPCs) and lower levels of bone formation. Among other things, this hypothesis would predict that introducing exogenous TGF-beta into old mice (growth factor replacement) should stimulate marrow CFU-f and increase bone formation. In the present study, we have tested this prediction and, indirectly the hypothesis, by injecting human recombinant TGF-beta1, i.p., into both young adult (4 month) and old mice (24 month). The effects of the growth factor on the skeleton were then assessed by measurements of trabecular bone volume, bone formation, fracture healing, and the number, proliferative, apoptotic, and alkaline phosphatase activity of marrow CFU-f/OPCs. Our data show that the introduction of 0.5 or 5.0 ug/day of TGF-beta1 into old mice for 20 days 1) increases trabecular bone volume, bone formation and the mineral apposition rate, 2) augments fracture healing, 3) increases the number and size of CFU-f colonies, and 4) increases proliferation and diminishes apoptosis of CFU-f in primary bone marrow cultures. Importantly, these stimulatory effects of injected growth factor are apparently age-specific, i.e., they are either not seen in young animals or, if seen, are found at much lower levels. While these observations do not exclude other possible mechanisms for the osteopenia of old mice, they provide further support for the hypothesis that, with age, diminished TGF-beta synthesis or availability results in a reduction in the marrow osteoprogenitor pool and bone formation. The findings also demonstrate that the latter changes can be reversed, at least transiently, by introducing exogenous TGF-beta1.