Mechanical load regulates bone growth via periosteal Osteocrin

Haruko Watanabe-Takano; Hiroki Ochi; Ayano Chiba; Ayaka Matsuo; Yugo Kanai; Shigetomo Fukuhara; Naoki Ito; Keisuke Sako; Takahiro Miyazaki; Kazuki Tainaka; Ichiro Harada; Shingo Sato; Yasuhiro Sawada; Naoto Minamino; Shu Takeda; Hiroki R. Ueda; Akihiro Yasoda; Naoki Mochizuki

Cell Reports (Jul 2021)

Mechanical load regulates bone growth via periosteal Osteocrin

Haruko Watanabe-Takano,
Hiroki Ochi,
Ayano Chiba,
Ayaka Matsuo,
Yugo Kanai,
Shigetomo Fukuhara,
Naoki Ito,
Keisuke Sako,
Takahiro Miyazaki,
Kazuki Tainaka,
Ichiro Harada,
Shingo Sato,
Yasuhiro Sawada,
Naoto Minamino,
Shu Takeda,
Hiroki R. Ueda,
Akihiro Yasoda,
Naoki Mochizuki

Affiliations

Haruko Watanabe-Takano: Department of Cell Biology, National Cerebral and Cardiovascular Center Research Institute, 6-1 Kishibe-shimmachi, Suita, Osaka 564-8565, Japan; Corresponding author
Hiroki Ochi: Department of Clinical Research, National Rehabilitation Center for Persons with Disabilities, 4-1 Namiki, Tokorozawa, Saitama 359-8555, Japan
Ayano Chiba: Department of Cell Biology, National Cerebral and Cardiovascular Center Research Institute, 6-1 Kishibe-shimmachi, Suita, Osaka 564-8565, Japan
Ayaka Matsuo: Omics Research Center, National Cerebral and Cardiovascular Center Research Institute, 6-1 Kishibe-shinmachi, Suita, Osaka 564-8565, Japan
Yugo Kanai: Department of Diabetes, Endocrinology and Nutrition, Graduate School of Medicine and Faculty of Medicine, Kyoto University, Yoshida-Konoe-cho, Sakyo-ku, Kyoto 606-8501, Japan
Shigetomo Fukuhara: Department of Molecular Pathophysiology, Institute of Advanced Medical Sciences, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-ku, Tokyo 113-8602, Japan
Naoki Ito: Laboratory of Molecular Life Science, Institute of Biomedical Research and Innovation, Foundation for Biomedical Research and Innovation at Kobe, 6-7-6 Minatojima-Minamimachi, Chuo-ku, Kobe 650-0047, Japan
Keisuke Sako: Department of Cell Biology, National Cerebral and Cardiovascular Center Research Institute, 6-1 Kishibe-shimmachi, Suita, Osaka 564-8565, Japan
Takahiro Miyazaki: Department of Cell Biology, National Cerebral and Cardiovascular Center Research Institute, 6-1 Kishibe-shimmachi, Suita, Osaka 564-8565, Japan
Kazuki Tainaka: Department of System Pathology for Neurological Disorders, Center for Bioresources, Brain Research Institute, Niigata University, 1-757 Asahimachidori, Chuo-ku, Niigata 951-8585, Japan
Ichiro Harada: Medical Products Technology, Development Center, R&D headquarters, Canon Inc., 3-30-2, Shimomaruko, Ohta-ku, Tokyo 146-8501, Japan
Shingo Sato: Center for Innovative Cancer Treatment, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519, Japan
Yasuhiro Sawada: Department of Cell Biology, National Cerebral and Cardiovascular Center Research Institute, 6-1 Kishibe-shimmachi, Suita, Osaka 564-8565, Japan; Department of Clinical Research, National Rehabilitation Center for Persons with Disabilities, 4-1 Namiki, Tokorozawa, Saitama 359-8555, Japan; Department of Rehabilitation for Motor Functions, National Rehabilitation Center for Persons with Disabilities, 4-1 Namiki, Tokorozawa, Saitama 359-8555, Japan
Naoto Minamino: Omics Research Center, National Cerebral and Cardiovascular Center Research Institute, 6-1 Kishibe-shinmachi, Suita, Osaka 564-8565, Japan
Shu Takeda: Division of Endocrinology, Toranomon Hospital Endocrine Center, 2-2-2 Toranomon, Minato-ku, Tokyo 105-8470, Japan
Hiroki R. Ueda: CREST, Japan Science and Technology Agency, 4-1-8 Honcho, Kawaguchi, Saitama 332-0012, Japan; Department of Systems Pharmacology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan; Laboratory for Synthetic Biology, RIKEN Center for Biosystems Dynamics Research, 1-3 Yamadaoka, Suita, Osaka 565-0871, Japan
Akihiro Yasoda: Clinical Research Center, National Hospital Organization Kyoto Medical Center, 1-1 Fukakusa-Mukaihatacho, Fushimi-ku, Kyoto 612-8555, Japan
Naoki Mochizuki: Department of Cell Biology, National Cerebral and Cardiovascular Center Research Institute, 6-1 Kishibe-shimmachi, Suita, Osaka 564-8565, Japan; CREST, Japan Science and Technology Agency, 4-1-8 Honcho, Kawaguchi, Saitama 332-0012, Japan; Corresponding author

Journal volume & issue: Vol. 36, no. 2
p. 109380

Abstract

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Summary: Mechanical stimuli including loading after birth promote bone growth. However, little is known about how mechanical force triggers biochemical signals to regulate bone growth. Here, we identified a periosteal-osteoblast-derived secretory peptide, Osteocrin (OSTN), as a mechanotransducer involved in load-induced long bone growth. OSTN produced by periosteal osteoblasts regulates growth plate growth by enhancing C-type natriuretic peptide (CNP)-dependent proliferation and maturation of chondrocytes, leading to elongation of long bones. Additionally, OSTN cooperates with CNP to regulate bone formation. CNP stimulates osteogenic differentiation of periosteal osteoprogenitors to induce bone formation. OSTN binds to natriuretic peptide receptor 3 (NPR3) in periosteal osteoprogenitors, thereby preventing NPR3-mediated clearance of CNP and consequently facilitating CNP-signal-mediated bone growth. Importantly, physiological loading induces Ostn expression in periosteal osteoblasts by suppressing Forkhead box protein O1 (FoxO1) transcription factor. Thus, this study reveals a crucial role of OSTN as a mechanotransducer converting mechanical loading to CNP-dependent bone formation.

Published in Cell Reports

ISSN: 2211-1247 (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Science: Biology (General)
Website: http://www.cell.com/cell-reports/home

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