Increased Bone Turnover and Possible Accelerated Fracture Healing in a Murine Model With an Increased Circulating C-Type Natriuretic Peptide
Increased Bone Turnover and Possible Accelerated Fracture Healing in a Murine Model With an Increased Circulating C-Type Natriuretic Peptide
复制标题
DOI：
10.1210/en.2014-1801
复制
发表时间：
2015-07-01
期刊：
影响因子：
4.8
通讯作者：
Nakao, Kazuwa
中科院分区：
文献类型：
--
作者：
Kondo, Eri;Yasoda, Akihiro;Nakao, Kazuwa
最近的研究表明，C型利钠肽（CNP）是一种有效的软骨内骨生长刺激剂。然而，CNP对骨转换的影响尚未得到充分研究。为了阐明这一问题，我们在本研究中研究了血浆CNP浓度升高的小鼠模型（SAP-CNP-Tg小鼠）的骨表型。显微计算机断层扫描（CT）分析显示，与野生型小鼠相比，年轻成年SAP-CNP-Tg小鼠股骨中的骨较少，但腰椎中没有。骨组织形态计量学从8周龄的SAP-CNP-Tg小鼠的胫骨表现出增强成骨细胞和成骨细胞的活动，根据骨钙素和抗酒石酸酸性磷酸酶-5b的血清水平升高，分别。接下来，我们使用8周龄SAP-CNP-Tg小鼠进行开放性和稳定性股骨骨折，并将愈合过程与年龄匹配的野生型小鼠进行比较。免疫组织化学研究显示，CNP及其受体，利钠肽受体-B和利钠肽清除受体，在野生型小鼠的硬骨痂中表达，表明CNP/利钠肽受体-B信号传导在骨折修复中的可能作用，特别是在骨重建阶段。在显微CT分析中，在SAP-CNP-Tg小鼠中观察到骨痂体积快速减少，随后产生显著更高的新骨体积，具有骨强度增加的趋势。此外，micro-CT分析还显示，SAP-CNP-Tg小鼠的骨重建加速，这也从SAP-CNP-Tg小鼠在骨折修复重建阶段血清骨钙素和抗酒石酸酸性磷酸酶-5b水平升高中得到证实。这些结果表明，CNP激活体内骨转换和重塑，并可能加速我们的小鼠模型中的骨折愈合。
Recent studies have revealed that C-type natriuretic peptide (CNP) is a potent stimulator of endochondral bone growth. Nevertheless, the effect of CNP on bone turnover has not yet been well studied. To elucidate this issue, we investigated the bone phenotype of a mouse model with elevated plasma CNP concentrations (SAP-CNP-Tg mice) in the present study. Microcomputed tomography (CT) analysis revealed less bone in femurs, but not in lumber vertebrae, of young adult SAP-CNP-Tg mice than that of wild-type mice. Bone histomorphometry of the tibiae from 8-week-old SAP-CNP-Tg mice showed enhanced osteoblastic and osteoclastic activities, in accordance with elevated serum levels of osteocalcin and tartrate-resistant acid phosphatase-5b, respectively. Next we performed an open and stabilized femoral fracture using 8-week-old SAP-CNP-Tg mice and compared the healing process with age-matched wild-type mice. An immunohistochemical study revealed that CNP and its receptors, natriuretic peptide receptor-B and natriuretic peptide clearance receptor, are expressed in hard calluses of wild-type mice, suggesting a possible role of CNP/natriuretic peptide receptor-B signaling in fracture repair, especially in bone remodeling stage. On micro-CT analysis, a rapid decrease in callus volume was observed in SAP-CNP-Tg mice, followed by a generation of significantly higher new bone volume with a tendency of increased bone strength. In addition, a micro-CT analysis also showed that bone remodeling was accelerated in SAP-CNP-Tg mice, which was also evident from increased serum osteocalcin and tartrate-resistant acid phosphatase-5b levels in SAP-CNP-Tg mice at the remodeling stage of fracture repair. These results indicate that CNP activates bone turnover and remodeling in vivo and possibly accelerates fracture healing in our mouse model.