C-TYPE NATRIURETIC PEPTIDE INCREASES BONE-RESORPTION IN 1,25-DIHYDROXYVITAMIN D-3 STIMULATED MOUSE BONE-MARROW CULTURES
C-TYPE NATRIURETIC PEPTIDE INCREASES BONE-RESORPTION IN 1,25-DIHYDROXYVITAMIN D-3 STIMULATED MOUSE BONE-MARROW CULTURES
复制标题
DOI：
10.1074/jbc.270.32.18983
复制
发表时间：
1995-08-11
影响因子：
4.8
通讯作者：
GLUCK, SL
中科院分区：
文献类型：
--
作者：
HOLLIDAY, LS;DEAN, AD;GLUCK, SL
大多数调节破骨细胞骨吸收的药物通过成骨细胞间接发挥作用，据报道，刺激可溶性鸟苷酸环化酶的一氧化氮通过cGMP非依赖性机制直接抑制破骨细胞骨吸收（1）。在这份报告中，我们证明了C型利钠肽（CNP），膜结合鸟苷酸环化酶的激活剂，刺激骨吸收的破骨细胞含有1，25-二羟维生素D-3（1，2 5-（OH）（2）D-3）刺激的小鼠骨髓培养。使用定量逆转录聚合酶链反应试验和抗CNP免疫细胞化学证明CNP在存在但不存在1，25-（OH）（2）D-3的情况下培养的小鼠骨髓细胞中表达。鸟苷酸环化酶B型（CNP受体）的mRNA在培养物中表达，不依赖于1，25-（OH）（2）D-3，CNP（1和10 μ M）使骨髓培养物中cGMP的产生分别增加到对照值的350和870%，10 μ M CNP增加破骨细胞骨吸收活性，通过鲸鱼牙本质薄片上的吸收面积测量，或从放射性标记的骨片中释放[H-3]脯氨酸，分别为对照的214和557%，而不影响破骨细胞的形成。骨髓培养物的骨吸收被7F9.1（一种抗CNP的单克隆抗体）抑制，但不被对照抗体抑制。这些结果表明，CNP是一种有效的破骨细胞活性激活剂，并可能是一种新的局部调节骨重建。
Most agents that regulate osteoclast bone resorption exert their effects indirectly, through the osteoblast, Nitric oxide, which stimulates soluble guanylyl cyclase, has been reported to inhibit osteoclast bone resorption directly, by a cGMP-independent mechanism (1). In this report, we demonstrate that C-type natriuretic peptide (CNP), an activator of membrane-bound guanylyl cyclase, stimulates bone resorption by osteoclast-containing 1,25-dihydroxyvitamin D-3 (1,2 5-(OH)(2)D-3)-stimulated mouse bone marrow cultures. Quantitative reverse transcription polymerase chain reaction assays and anti-CNP immunocytochemistry were used to demonstrate that CNP is expressed in mouse marrow cells cultured in the presence, but not the absence, of 1,25-(OH)(2)D-3. mRNA for guanylyl cyclase type B, the receptor for CNP, was expressed in cultures independent of 1,25-(OH)(2)D-3, CNP (1 and 10 mu M) elevated cGMP production in marrow cultures to 350 and 870%, respectively, of control values, 10 mu M CNP increased osteoclast bone resorptive activity, measured by the resorption area on whale dentine wafers, or by the NH4Cl-inhibitable release of [H-3]proline from radiolabeled bone chips, to 214 and 557% of control, respectively, without affecting osteoclast formation, Bone resorption by the marrow cultures was inhibited by 7F9.1, a monoclonal antibody raised against CNP, but not by control antibodies. These results indicate that CNP is a potent activator of osteoclast activity and may be a novel local regulator of bone remodeling.