Regulation of fetal rat bone growth by C-type natriuretic peptide and cGMP
Regulation of fetal rat bone growth by C-type natriuretic peptide and cGMP
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DOI：
10.1203/00006450-200002000-00007
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发表时间：
2000-02-01
影响因子：
3.6
通讯作者：
Baron, J
中科院分区：
文献类型：
--
作者：
Mericq, V;Uyeda, JA;Baron, J
c型利钠肽（CNP）及其高亲和力受体b在胎儿骨骼中表达。本研究表明，CNP通过几种机制加速了器官培养中胎鼠跖骨的纵向生长。首先，CNP刺激增殖区软骨细胞增殖，通过[H-3]胸苷结合来评估。其次，通过定量组织学评估，CNP刺激细胞肥大。第三，通过将(SO4)-S-35掺入糖胺聚糖中，CNP刺激软骨基质的生成。利钠肽受体- b含有胞内胍基环化酶催化结构域。因此，我们假设环GMP （cGMP）可以复制CNP对胎儿骨骼的影响。与这一假设一致，我们发现8-Br-cGMP与CNP一样，刺激纵向生长和糖胺聚糖合成。然而，与CNP不同，cGMP抑制生长板软骨细胞的增殖，对肥大无影响。我们得出结论，CNP通过增加软骨细胞增殖、软骨细胞肥大和软骨基质生成来刺激纵向骨生长。cGMP是CNP的第二信使，它复制了CNP的部分作用，但不是全部作用，这表明其他信号转导机制也可能参与其中。
C-type natriuretic peptide (CNP) and its high affinity receptor-B are expressed in fetal bones. Here we show that CNP accelerates longitudinal growth of fetal rat metatarsal bones in organ culture by several mechanisms. First, CNP stimulates chondrocyte proliferation in the proliferative zone as assessed by [H-3]thymidine incorporation. Second, CNP stimulates cell hypertrophy as assessed by quantitative histology. Third, CNP stimulates cartilage matrix production as assessed by incorporation of (SO4)-S-35 into glycosaminoglycans. Natriuretic peptide receptor-B contains an intracellular guanylyl cyclase catalytic domain. We therefore hypothesized that cyclic GMP (cGMP) would reproduce the effects of CNP on fetal bones. Consistent with this hypothesis, we found that 8-Br-cGMP, like CNP, stimulates longitudinal growth and glycosaminoglycan synthesis. However, unlike CNP, cGMP inhibits proliferation of growth plate chondrocytes and has no effect on hypertrophy. We conclude that CNP stimulates longitudinal bone growth by increasing chondrocyte proliferation, chondrocyte hypertrophy, and cartilage matrix production. cGMP, a second messenger for CNP, reproduces some but not all of the effects of CNP, suggesting that other signal transduction mechanisms may also be involved.