SLPI is a critical mediator that controls PTH-induced bone formation

Akito Morimoto, Junichi Kikuta (), Keizo Nishikawa, Takao Sudo, Maki Uenaka, Masayuki Furuya, Tetsuo Hasegawa, Kunihiko Hashimoto, Hiroyuki Tsukazaki, Shigeto Seno, Akira Nakamura, Daisuke Okuzaki, Fuminori Sugihara, Akinori Ninomiya, Takeshi Yoshimura, Ryoko Takao-Kawabata, Hideo Matsuda and Masaru Ishii ()
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Akito Morimoto: Graduate School of Medicine and Frontier Biosciences, Osaka University
Junichi Kikuta: Graduate School of Medicine and Frontier Biosciences, Osaka University
Keizo Nishikawa: Graduate School of Medicine and Frontier Biosciences, Osaka University
Takao Sudo: Graduate School of Medicine and Frontier Biosciences, Osaka University
Maki Uenaka: Graduate School of Medicine and Frontier Biosciences, Osaka University
Masayuki Furuya: Graduate School of Medicine and Frontier Biosciences, Osaka University
Tetsuo Hasegawa: Graduate School of Medicine and Frontier Biosciences, Osaka University
Kunihiko Hashimoto: Graduate School of Medicine and Frontier Biosciences, Osaka University
Hiroyuki Tsukazaki: Graduate School of Medicine and Frontier Biosciences, Osaka University
Shigeto Seno: Graduate School of Information Science and Technology, Osaka University
Akira Nakamura: Tohoku Medical and Pharmaceutical University
Daisuke Okuzaki: Osaka University
Fuminori Sugihara: Immunology Frontier Research Center and Research Institute for Microbial Diseases, Osaka University
Akinori Ninomiya: Immunology Frontier Research Center and Research Institute for Microbial Diseases, Osaka University
Takeshi Yoshimura: Asahi Kasei Pharma Corporation
Ryoko Takao-Kawabata: Asahi Kasei Pharma Corporation
Hideo Matsuda: Graduate School of Information Science and Technology, Osaka University
Masaru Ishii: Graduate School of Medicine and Frontier Biosciences, Osaka University

Nature Communications, 2021, vol. 12, issue 1, 1-14

Abstract: Abstract Osteoclastic bone resorption and osteoblastic bone formation/replenishment are closely coupled in bone metabolism. Anabolic parathyroid hormone (PTH), which is commonly used for treating osteoporosis, shifts the balance from osteoclastic to osteoblastic, although it is unclear how these cells are coordinately regulated by PTH. Here, we identify a serine protease inhibitor, secretory leukocyte protease inhibitor (SLPI), as a critical mediator that is involved in the PTH-mediated shift to the osteoblastic phase. Slpi is highly upregulated in osteoblasts by PTH, while genetic ablation of Slpi severely impairs PTH-induced bone formation. Slpi induction in osteoblasts enhances its differentiation, and increases osteoblast–osteoclast contact, thereby suppressing osteoclastic function. Intravital bone imaging reveals that the PTH-mediated association between osteoblasts and osteoclasts is disrupted in the absence of SLPI. Collectively, these results demonstrate that SLPI regulates the communication between osteoblasts and osteoclasts to promote PTH-induced bone anabolism.

Date: 2021
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DOI: 10.1038/s41467-021-22402-x

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