Regulation of growth plate chondrogenesis by bone morphogenetic protein-2.
Regulation of growth plate chondrogenesis by bone morphogenetic protein-2.
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DOI：
10.1210/endo.142.1.7901
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发表时间：
2001
期刊：
影响因子：
4.8
通讯作者：
Francesco De Luca;Kevin M. Barnes;Jennifer A. Uyeda;Stacy De-Levi;V. Abad;T. Palese;Verónica Mericq;Jeffrey Baron
中科院分区：
文献类型：
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作者：
Francesco De Luca;Kevin M. Barnes;Jennifer A. Uyeda;Stacy De-Levi;V. Abad;T. Palese;Verónica Mericq;Jeffrey Baron
骨形态发生蛋白（BMPs）调控胚胎骨骼发育。我们假设生长板中表达的BMP-2也调节生长板软骨形成和纵向骨生长。为了验证这一假设，将胎鼠跖骨在重组人BMP-2存在下培养3天。BMP-2的加入导致跖骨纵向生长的浓度依赖性加速。由于纵向骨生长的速度主要取决于生长板软骨形成的速度，我们研究了它的三个主要组成部分。通过[(3)H]胸腺嘧啶掺入评估，BMP-2刺激生长板骨骺区的软骨细胞增殖。通过定量组织学和酶组织化学评估，BMP-2也引起软骨细胞肥大的增加。通过将（35）SO(4)掺入糖胺聚糖来评估，对软骨基质合成的刺激作用仅在最高浓度的BMP-2下产生。这些BMP-2介导的刺激作用被重组人Noggin（一种阻断BMP-2作用的糖蛋白）逆转。在缺乏外源性BMP-2的情况下，Noggin抑制跖骨纵向生长、软骨细胞增殖和软骨细胞肥大，这表明内源性bmp刺激骨纵向生长和软骨形成。我们认为BMP-2通过刺激生长板软骨细胞增殖和软骨细胞肥大来加速纵向骨生长。
Bone morphogenetic proteins (BMPs) regulate embryonic skeletal development. We hypothesized that BMP-2, which is expressed in the growth plate, also regulates growth plate chondrogenesis and longitudinal bone growth. To test this hypothesis, fetal rat metatarsal bones were cultured for 3 days in the presence of recombinant human BMP-2. The addition of BMP-2 caused a concentration-dependent acceleration of metatarsal longitudinal growth. As the rate of longitudinal bone growth depends primarily on the rate of growth plate chondrogenesis, we studied each of its three major components. BMP-2 stimulated chondrocyte proliferation in the epiphyseal zone of the growth plate, as assessed by [(3)H]thymidine incorporation. BMP-2 also caused an increase in chondrocyte hypertrophy, as assessed by quantitative histology and enzyme histochemistry. A stimulatory effect on cartilage matrix synthesis, assessed by (35)SO(4) incorporation into glycosaminoglycans, was produced only by the highest concentration of BMP-2. These BMP-2-mediated stimulatory effects were reversed by recombinant human Noggin, a glycoprotein that blocks BMP-2 action. In the absence of exogenous BMP-2, Noggin inhibited metatarsal longitudinal growth, chondrocyte proliferation, and chondrocyte hypertrophy, which suggests that endogenous BMPs stimulate longitudinal bone growth and chondrogenesis. We conclude that BMP-2 accelerates longitudinal bone growth by stimulating growth plate chondrocyte proliferation and chondrocyte hypertrophy.