Barnes K M, Uyeda J A, De-Levi S, Abad V, Palese T, Mericq V, Baron J
Division of Pediatric Endocrinology, Department of Pediatrics, University of Maryland School of Medicine, Baltimore, Maryland 21201-1595, USA.
Endocrinology. 2001 Jan;142(1):430-6. doi: 10.1210/endo.142.1.7901.
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.
骨形态发生蛋白（BMPs）调节胚胎骨骼发育。我们推测，在生长板中表达的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存在的情况下培养3天。添加BMP-2导致跖骨纵向生长呈浓度依赖性加速。由于纵向骨生长速率主要取决于生长板软骨形成速率，我们研究了其三个主要组成部分中的每一个。通过[³H]胸苷掺入评估，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还导致软骨细胞肥大增加。仅最高浓度的BMP-2对软骨基质合成有刺激作用，通过³⁵SO₄掺入糖胺聚糖来评估。重组人Noggin可逆转这些BMP-2介导的刺激作用，Noggin是一种可阻断BMP-2作用的糖蛋白。在没有外源性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BMPs刺激纵向骨生长和软骨形成。我们得出结论，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。
