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首页> 外文期刊>Journal of bone and mineral research: the official journal of the American Society for Bone and Mineral Research >Overexpression of BCLXL in Osteoblasts Inhibits Osteoblast Apoptosis and Increases Bone Volume and Strength
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Overexpression of BCLXL in Osteoblasts Inhibits Osteoblast Apoptosis and Increases Bone Volume and Strength

机译：BCLXL在成骨细胞中的过量表达抑制成骨细胞凋亡并增加骨量和强度

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The Bcl2 family proteins, Bcl2 and BclXL, suppress apoptosis by preventing the release of caspase activators from mitochondria through the inhibition of Bax subfamily proteins. We reported that BCL2 overexpression in osteoblasts using the 2.3 kb Col1a1 promoter increased osteoblast proliferation, failed to reduce osteoblast apoptosis, inhibited osteoblast maturation, and reduced the number of osteocyte processes, leading to massive osteocyte death. We generated BCLXL (BCL2L1) transgenic mice using the same promoter to investigate BCLXL functions in bone development and maintenance. Bone mineral density in the trabecular bone of femurs was increased, whereas that in the cortical bone was similar to that in wild-type mice. Osteocyte process formation was unaffected and bone structures were similar to those in wild-type mice. A micro-CT analysis showed that trabecular bone volume in femurs and vertebrae and the cortical thickness of femurs were increased. A dynamic bone histomorphometric analysis revealed that the mineralizing surface was larger in trabecular bone, and the bone-formation rate was increased in cortical bone. Serum osteocalcin but not TRAP5b was increased, BrdU-positive osteoblastic cell numbers were increased, TUNEL-positive osteoblastic cell numbers were reduced, and osteoblast marker gene expression was enhanced in BCLXL transgenic mice. The three-point bending test indicated that femurs were stronger in BCLXL transgenic mice than in wild-type mice. The frequency of TUNEL-positive primary osteoblasts was lower in BCLXL transgenic mice than in wild-type mice during cultivation, and osteoblast differentiation was enhanced but depended on cell density, indicating that enhanced differentiation was mainly owing to reduced apoptosis. Increased trabecular and cortical bone volumes were maintained during aging in male and female mice. These results indicate that BCLXL overexpression in osteoblasts increased the trabecular and cortical bone volumes with normal structures and maintained them majorly by preventing osteoblast apoptosis, implicating BCLXL as a therapeutic target of osteoporosis. (C) 2016 American Society for Bone and Mineral Research.
机译：Bcl2家族蛋白Bcl2和BclXL通过抑制Bax亚家族蛋白，阻止caspase激活剂从线粒体中释放，从而抑制细胞凋亡。我们报告说，使用2.3 kb Col1a1启动子在成骨细胞中BCL2过表达增加了成骨细胞增殖，未能减少成骨细胞凋亡，抑制了成骨细胞成熟，并减少了成骨细胞的数量，导致大量的成骨细胞死亡。我们使用相同的启动子生成了BCLXL（BCL2L1）转基因小鼠，以研究BCLXL在骨骼发育和维持中的功能。股骨小梁骨的骨矿物质密度增加，而皮质骨的骨矿物质密度与野生型小鼠相似。骨细胞过程的形成不受影响，骨骼结构与野生型小鼠相似。显微CT分析显示，股骨和椎骨的小梁骨体积和股骨皮质厚度增加。动态骨组织形态分析表明，小梁骨的矿化表面较大，而皮质骨的骨形成率增加。在BCLXL转基因小鼠中，血清骨钙素增加而不是TRAP5b增加，BrdU阳性成骨细胞数目增加，TUNEL阳性成骨细胞数目减少，成骨细胞标志物基因表达增强。三点弯曲试验表明，BCLXL转基因小鼠的股骨比野生型小鼠的股骨更强。在培养过程中，BCLXL转基因小鼠中TUNEL阳性原代成骨细胞的频率低于野生型小鼠，并且成骨细胞分化得到增强，但取决于细胞密度，这表明增强的分化主要是由于凋亡减少。在雄性和雌性小鼠的衰老过程中，小梁和皮质骨的体积增加。这些结果表明，成骨细胞中BCLXL的过表达增加了具有正常结构的小梁和皮质骨的体积，并主要通过防止成骨细胞的凋亡来维持它们，这暗示了BCLXL是骨质疏松的治疗靶标。 （C）2016美国骨矿物质研究学会。

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