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

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

Journal Nat. Commun. (2021)
Title SLPI is a critical mediator that controls PTH-induced bone formation
Laboratory Laboratory of Immunology and Cell Biology〈Prof. ISHII Masaru〉
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.

Authors

Akito Morimoto (1, 2), Junichi Kikuta (1, 2, 3), Keizo Nishikawa (1, 2), Takao Sudo (1, 2), Maki Uenaka (1, 2), Masayuki Furuya (1, 2), Tetsuo Hasegawa (1, 2), Kunihiko Hashimoto (1, 2), Hiroyuki Tsukazaki (1, 2), Shigeto Seno (4), Akira Nakamura (5), Daisuke Okuzaki (2, 6), Fuminori Sugihara (7), Akinori Ninomiya (7), Takeshi Yoshimura (8), Ryoko Takao-Kawabata (9), Hideo Matsuda (4), Masaru Ishii (1, 2, 3)

  1. Department of Immunology and Cell Biology, Graduate School of Medicine and Frontier Biosciences, Osaka University, Osaka, Japan.
  2. WPI-Immunology Frontier Research Center, Osaka University, Osaka, Japan.
  3. Laboratory of Bioimaging and Drug Discovery, National Institutes of Biomedical Innovation, Health and Nutrition, Osaka, Japan.
  4. Department of Bioinformatic Engineering, Graduate School of Information Science and Technology, Osaka University, Osaka, Japan.
  5. Division of Immunology, Tohoku Medical and Pharmaceutical University, Miyagi, Japan.
  6. Genome Information Research Center, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan.
  7. Core Instrumentation Facility, Immunology Frontier Research Center and Research Institute for Microbial Diseases, Osaka University, Osaka, Japan.
  8. Medical Affairs Department, Asahi Kasei Pharma Corporation, Tokyo, Japan.
  9. Laboratory for Pharmacology, Pharmaceuticals Research Center, Asahi Kasei Pharma Corporation, Tokyo, Japan.
PubMed 33837198

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