Bone Formation Is Coupled to Resorption Via Suppression of Sclerostin Expression by Osteoclasts |
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| Authors: | Masanori Koide Yasuhiro Kobayashi Teruhito Yamashita Shunsuke Uehara Midori Nakamura B. Yukihiro Hiraoka Yuki Ozaki Tadahiro Iimura Hisataka Yasuda Naoyuki Takahashi Nobuyuki Udagawa |
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| Affiliation: | 1. Institute for Oral Science, Matsumoto Dental University, Shiojiri, Japan;2. Department of Biochemistry, Matsumoto Dental University, Shiojiri, Japan;3. Department of Chemistry, Matsumoto Dental University, Shiojiri, Japan;4. Proteo‐Science Center (PROS) and Advanced Research Support Center (ADRES), Ehime University, and Translational Research Center and Artificial Joint Integrated Center, Ehime University Hospital Shitsukawa, Toon, Japan;5. Nagahama Institute for Biochemical Science, Oriental Yeast Co., Ltd., Nagahama, Japan |
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| Abstract: | Bone formation is coupled to bone resorption throughout life. However, the coupling mechanisms are not fully elucidated. Using Tnfrsf11b‐deficient (OPG–/–) mice, in which bone formation is clearly coupled to bone resorption, we found here that osteoclasts suppress the expression of sclerostin, a Wnt antagonist, thereby promoting bone formation. Wnt/β‐catenin signals were higher in OPG–/– and RANKL‐transgenic mice with a low level of sclerostin. Conditioned medium from osteoclast cultures (Ocl‐CM) suppressed sclerostin expression in UMR106 cells and osteocyte cultures. In vitro experiments revealed that osteoclasts secreted leukemia inhibitory factor (LIF) and inhibited sclerostin expression. Anti‐RANKL antibodies, antiresorptive agents, suppressed LIF expression and increased sclerostin expression, thereby reducing bone formation in OPG–/– mice. Taken together, osteoclast‐derived LIF regulates bone turnover through sclerostin expression. Thus, LIF represents a target for improving the prolonged suppression of bone turnover by antiresorptive agents. © 2017 The Authors. Journal of Bone and Mineral Research Published by Wiley Periodicals Inc. |
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| Keywords: | MOLECULAR PATHWAYS‐REMODELING OSTEOBLASTS OSTEOCLASTS OSTEOCYTES WNT/BETA‐CATENIN/LRPS |
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