Overexpression of BMP-2 and BMP-4 alters the size and shape of developing skeletal elements in the chick limb

Overexpression of BMP-2 and BMP-4 alters the size and shape of developing skeletal elements in the chick limb
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DOI:
10.1016/0925-4773(96)00540-0
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发表时间:
1996-07-01
影响因子:
2.6
通讯作者:
FrancisWest, PH
FrancisWest, PH
中科院分区:
生物学4区
文献类型:
--
作者:
Duprez, D;Bella, EJD;FrancisWest, PH

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骨形态发生蛋白是转化生长因子β(TGF β)超家族的成员,其参与一系列发育过程,包括骨骼的建模。我们在这里表明,BMP-2在发育中的鸡肢早期软骨凝聚周围的间充质中表达,BMP-4在软骨膜中表达的发展中的软骨元素。为了研究它们在软骨发育过程中的作用,使用逆转录病毒载体在发育中的鸡肢中异位表达BMP-2和BMP-4。BMP-2或BMP-4的过度表达导致软骨元素体积的急剧增加,改变它们的形状并导致关节融合。这种体积的增加似乎是由于基质量和软骨细胞数量的增加。后者似乎不是由于软骨细胞增殖增加,这表明它可能是由于增加前体的募集。BMP-2和BMP-4也延迟了软骨细胞的肥大和成骨骨膜的形成。这些数据提供了BMP-2和BMP-LF如何在正常胚胎发育过程中建模和控制骨骼元素生长的见解,表明这两种分子在招募非软骨形成前体到软骨形成命运中的作用。
Bone morphogenetic proteins are members of the transforming growth factor beta (TGF beta) superfamily which are involved in a range of developmental processes including modelling of the skeleton. We show here that Bmp-2 is expressed in mesenchyme surrounding early cartilage condensations in the developing chick limb, and that Bmp-4 is expressed in the perichondrium of developing cartilage elements. To investigate their roles during cartilage development, BMP-2 and BMP-4 were expressed ectopically in developing chick limbs using retroviral vectors. Over-expression of BMP-2 or BMP-4 led to a dramatic increase in the volume of cartilage elements, altered their shapes and led to joint fusions. This increase in volume appeared to result from an increase in the amount of matrix and in the number of chondrocytes. The latter did not appear to be due to increased proliferation of chondrocytes, suggesting that it may result from increased recruitment of precursors. BMP-2 and BMP-4 also delayed hypertrophy of chondrocytes and formation of the osteogenic periosteum. These data provide insights into how BMP-2 and BMP-LF may model and control the growth of skeletal elements during normal embryonic development, suggesting roles for both molecules in recruiting non-chondrogenic precursors to chondrogenic fate.