Increased expression of TGF-beta 2 in osteoblasts results in an osteoporosis-like phenotype.
Increased expression of TGF-beta 2 in osteoblasts results in an osteoporosis-like phenotype.
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成骨细胞中 TGF-β2 表达增加会导致骨质疏松症样表型。
DOI：
10.1083/jcb.132.1.195
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发表时间：
1996-01
期刊：
影响因子：
--
通讯作者：
Derynck R
中科院分区：
文献类型：
--
作者：
Erlebacher A;Derynck R
骨骼的发育需要成骨细胞和骨吸收破骨细胞的协调活动。这两种细胞的活性可能受到转化生长因子-β的调节，转化生长因子-β在骨基质中含量丰富。我们已经使用转基因小鼠来评估转化生长因子-β2在骨发育和转换中的作用。来自骨钙素启动子的成骨细胞特异性过度表达的转化生长因子-β2导致进行性骨丢失，与成骨基质沉积和破骨细胞性骨吸收增加相关。这种表型与人类甲状旁腺功能亢进症和骨质疏松症的骨骼异常非常相似。此外，高水平的转化生长因子-β2过度表达导致骨矿化缺陷和锁骨严重发育不良，这是发育性疾病锁骨颅骨发育不良的标志。我们的结果提示，转化生长因子-β2是骨重建的局部正向调节因子，骨细胞合成转化生长因子-β2的改变，或其对转化生长因子-β2的反应性改变，可能参与代谢性骨病的发病。
The development of the skeleton requires the coordinated activities of bone-forming osteoblasts and bone-resorbing osteoclasts. The activities of these two cell types are likely to be regulated by TGF-beta, which is abundant in bone matrix. We have used transgenic mice to evaluate the role of TGF-beta 2 in bone development and turnover. Osteoblast- specific overexpression of TGF-beta 2 from the osteocalcin promoter resulted in progressive bone loss associated with increases in osteoblastic matrix deposition and osteoclastic bone resorption. This phenotype closely resembles the bone abnormalities seen in human hyperparathyroidism and osteoporosis. Furthermore, a high level of TGF- beta 2 overexpression resulted in defective bone mineralization and severe hypoplasia of the clavicles, a hallmark of the developmental disease cleidocranial dysplasia. Our results suggest that TGF-beta 2 functions as a local positive regulator of bone remodeling and that alterations in TGF-beta 2 synthesis by bone cells, or in their responsiveness to TGF-beta 2, may contribute to the pathogenesis of metabolic bone disease.