Increased Bone Turnover and Possible Accelerated Fracture Healing in a Murine Model With an Increased Circulating C-Type Natriuretic Peptide

Endocrinology - Tập 156 Số 7 - Trang 2518-2529 - 2015
Eri Kondo1, Akihiro Yasoda1, Toshihito Fujii1, Kazumasa Nakao1,2, Yui Yamashita1, Yoriko Ueda-Sakane1, Naotetsu Kanamoto1, Masako Miura1, Hiroshi Arai3, Masashi Mukoyama4, Nobuya Inagaki1, Kazuwa Nakao5
1Departments of Diabetes, Endocrinology, and Nutrition (E.K., A.Y., T.F., Y.Y., Y.U.-S., N.K., M.M., N.I.), Kyoto University Graduate School of Medicine, 606-8507 Kyoto, Japan
2Maxillofacial Surgery (Kazum. N.), Kyoto University Graduate School of Medicine, 606-8507 Kyoto, Japan
3Health Care Service Center (H.A.), Kyoto Institute of Technology, Matsugasaki-Hashikami-cho, 606-8585 Kyoto, Japan
4Department of Nephrology (M.K.), Graduate School of Medical Science, Kumamoto University, 860-8556 Kumamoto City, Japan
5Medical Innovation Center (Kazuw. N.), Kyoto University Graduate School of Medicine, 606-8507 Kyoto, Japan

Tóm tắt

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.

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Endocrinology

Tập 156 Số 7

2518-2529

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