title: Increased Bone Turnover and Possible Accelerated Fracture Healing in a Murine Model With an Increased Circulating C-Type Natriuretic Peptide.
abstract: 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.
authors: Departments of Diabetes, Endocrinology, and Nutrition (E.K., A.Y., T.F., Y.Y., Y.U.-S., N.K., M.M., N.I.) and Maxillofacial Surgery (Kazum. N.) and Medical Innovation Center (Kazuw. N.), Kyoto University Graduate School of Medicine, 606-8507 Kyoto, Japan; Health Care Service Center (H.A.), Kyoto Institute of Technology, Matsugasaki-Hashikami-cho, 606-8585 Kyoto, Japan; and Department of Nephrology (M.K.), Graduate School of Medical Science, Kumamoto University, 860-8556 Kumamoto City, Japan.
authors: Eri
authors: E
authors: Kondo
authors: Departments of Diabetes, Endocrinology, and Nutrition (E.K., A.Y., T.F., Y.Y., Y.U.-S., N.K., M.M., N.I.) and Maxillofacial Surgery (Kazum. N.) and Medical Innovation Center (Kazuw. N.), Kyoto University Graduate School of Medicine, 606-8507 Kyoto, Japan; Health Care Service Center (H.A.), Kyoto Institute of Technology, Matsugasaki-Hashikami-cho, 606-8585 Kyoto, Japan; and Department of Nephrology (M.K.), Graduate School of Medical Science, Kumamoto University, 860-8556 Kumamoto City, Japan.
authors: Akihiro
authors: A
authors: Yasoda
authors: Departments of Diabetes, Endocrinology, and Nutrition (E.K., A.Y., T.F., Y.Y., Y.U.-S., N.K., M.M., N.I.) and Maxillofacial Surgery (Kazum. N.) and Medical Innovation Center (Kazuw. N.), Kyoto University Graduate School of Medicine, 606-8507 Kyoto, Japan; Health Care Service Center (H.A.), Kyoto Institute of Technology, Matsugasaki-Hashikami-cho, 606-8585 Kyoto, Japan; and Department of Nephrology (M.K.), Graduate School of Medical Science, Kumamoto University, 860-8556 Kumamoto City, Japan.
authors: Toshihito
authors: T
authors: Fujii
authors: Departments of Diabetes, Endocrinology, and Nutrition (E.K., A.Y., T.F., Y.Y., Y.U.-S., N.K., M.M., N.I.) and Maxillofacial Surgery (Kazum. N.) and Medical Innovation Center (Kazuw. N.), Kyoto University Graduate School of Medicine, 606-8507 Kyoto, Japan; Health Care Service Center (H.A.), Kyoto Institute of Technology, Matsugasaki-Hashikami-cho, 606-8585 Kyoto, Japan; and Department of Nephrology (M.K.), Graduate School of Medical Science, Kumamoto University, 860-8556 Kumamoto City, Japan.
authors: Kazumasa
authors: K
authors: Nakao
authors: Departments of Diabetes, Endocrinology, and Nutrition (E.K., A.Y., T.F., Y.Y., Y.U.-S., N.K., M.M., N.I.) and Maxillofacial Surgery (Kazum. N.) and Medical Innovation Center (Kazuw. N.), Kyoto University Graduate School of Medicine, 606-8507 Kyoto, Japan; Health Care Service Center (H.A.), Kyoto Institute of Technology, Matsugasaki-Hashikami-cho, 606-8585 Kyoto, Japan; and Department of Nephrology (M.K.), Graduate School of Medical Science, Kumamoto University, 860-8556 Kumamoto City, Japan.
authors: Yui
authors: Y
authors: Yamashita
authors: Departments of Diabetes, Endocrinology, and Nutrition (E.K., A.Y., T.F., Y.Y., Y.U.-S., N.K., M.M., N.I.) and Maxillofacial Surgery (Kazum. N.) and Medical Innovation Center (Kazuw. N.), Kyoto University Graduate School of Medicine, 606-8507 Kyoto, Japan; Health Care Service Center (H.A.), Kyoto Institute of Technology, Matsugasaki-Hashikami-cho, 606-8585 Kyoto, Japan; and Department of Nephrology (M.K.), Graduate School of Medical Science, Kumamoto University, 860-8556 Kumamoto City, Japan.
authors: Yoriko
authors: Y
authors: Ueda-Sakane
authors: Departments of Diabetes, Endocrinology, and Nutrition (E.K., A.Y., T.F., Y.Y., Y.U.-S., N.K., M.M., N.I.) and Maxillofacial Surgery (Kazum. N.) and Medical Innovation Center (Kazuw. N.), Kyoto University Graduate School of Medicine, 606-8507 Kyoto, Japan; Health Care Service Center (H.A.), Kyoto Institute of Technology, Matsugasaki-Hashikami-cho, 606-8585 Kyoto, Japan; and Department of Nephrology (M.K.), Graduate School of Medical Science, Kumamoto University, 860-8556 Kumamoto City, Japan.
authors: Naotetsu
authors: N
authors: Kanamoto
authors: Departments of Diabetes, Endocrinology, and Nutrition (E.K., A.Y., T.F., Y.Y., Y.U.-S., N.K., M.M., N.I.) and Maxillofacial Surgery (Kazum. N.) and Medical Innovation Center (Kazuw. N.), Kyoto University Graduate School of Medicine, 606-8507 Kyoto, Japan; Health Care Service Center (H.A.), Kyoto Institute of Technology, Matsugasaki-Hashikami-cho, 606-8585 Kyoto, Japan; and Department of Nephrology (M.K.), Graduate School of Medical Science, Kumamoto University, 860-8556 Kumamoto City, Japan.
authors: Masako
authors: M
authors: Miura
authors: Departments of Diabetes, Endocrinology, and Nutrition (E.K., A.Y., T.F., Y.Y., Y.U.-S., N.K., M.M., N.I.) and Maxillofacial Surgery (Kazum. N.) and Medical Innovation Center (Kazuw. N.), Kyoto University Graduate School of Medicine, 606-8507 Kyoto, Japan; Health Care Service Center (H.A.), Kyoto Institute of Technology, Matsugasaki-Hashikami-cho, 606-8585 Kyoto, Japan; and Department of Nephrology (M.K.), Graduate School of Medical Science, Kumamoto University, 860-8556 Kumamoto City, Japan.
authors: Hiroshi
authors: H
authors: Arai
authors: Departments of Diabetes, Endocrinology, and Nutrition (E.K., A.Y., T.F., Y.Y., Y.U.-S., N.K., M.M., N.I.) and Maxillofacial Surgery (Kazum. N.) and Medical Innovation Center (Kazuw. N.), Kyoto University Graduate School of Medicine, 606-8507 Kyoto, Japan; Health Care Service Center (H.A.), Kyoto Institute of Technology, Matsugasaki-Hashikami-cho, 606-8585 Kyoto, Japan; and Department of Nephrology (M.K.), Graduate School of Medical Science, Kumamoto University, 860-8556 Kumamoto City, Japan.
authors: Masashi
authors: M
authors: Mukoyama
authors: Departments of Diabetes, Endocrinology, and Nutrition (E.K., A.Y., T.F., Y.Y., Y.U.-S., N.K., M.M., N.I.) and Maxillofacial Surgery (Kazum. N.) and Medical Innovation Center (Kazuw. N.), Kyoto University Graduate School of Medicine, 606-8507 Kyoto, Japan; Health Care Service Center (H.A.), Kyoto Institute of Technology, Matsugasaki-Hashikami-cho, 606-8585 Kyoto, Japan; and Department of Nephrology (M.K.), Graduate School of Medical Science, Kumamoto University, 860-8556 Kumamoto City, Japan.
authors: Nobuya
authors: N
authors: Inagaki
authors: Departments of Diabetes, Endocrinology, and Nutrition (E.K., A.Y., T.F., Y.Y., Y.U.-S., N.K., M.M., N.I.) and Maxillofacial Surgery (Kazum. N.) and Medical Innovation Center (Kazuw. N.), Kyoto University Graduate School of Medicine, 606-8507 Kyoto, Japan; Health Care Service Center (H.A.), Kyoto Institute of Technology, Matsugasaki-Hashikami-cho, 606-8585 Kyoto, Japan; and Department of Nephrology (M.K.), Graduate School of Medical Science, Kumamoto University, 860-8556 Kumamoto City, Japan.
authors: Kazuwa
authors: K
authors: Nakao
mesh_terms: D000818:Animals; D016723:Bone Remodeling / Q000235:genetics*; D001842:Bone and Bones / Q000378:metabolism*; D002146:Bony Callus / Q000378:metabolism; D005269:Femur / Q000000981:diagnostic imaging / Q000378:metabolism*; D017102:Fracture Healing / Q000235:genetics*; D006801:Humans; D008159:Lumbar Vertebrae / Q000000981:diagnostic imaging / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D023421:Models, Animal; D020098:Natriuretic Peptide, C-Type / Q000235:genetics* / Q000378:metabolism; D010006:Osteoblasts / Q000378:metabolism; D010010:Osteoclasts / Q000378:metabolism; D011401:Promoter Regions, Genetic; D017461:Receptors, Atrial Natriuretic Factor / Q000378:metabolism; D000683:Serum Amyloid P-Component / Q000235:genetics; D015398:Signal Transduction; D013977:Tibia / Q000378:metabolism* / Q000473:pathology; D055114:X-Ray Microtomography; D000099242:Atrial Natriuretic Factor Receptor B
chemical_list: D020098:Natriuretic Peptide, C-Type; D017461:Receptors, Atrial Natriuretic Factor; D000683:Serum Amyloid P-Component; D000099242:Atrial Natriuretic Factor Receptor B; C073616:atrial natriuretic factor receptor C