RRC ID 65563
Author Morimoto A, Kikuta J, Nishikawa K, Sudo T, Uenaka M, Furuya M, Hasegawa T, Hashimoto K, Tsukazaki H, Seno S, Nakamura A, Okuzaki D, Sugihara F, Ninomiya A, Yoshimura T, Takao-Kawabata R, Matsuda H, Ishii M.
Title SLPI is a critical mediator that controls PTH-induced bone formation.
Journal Nat Commun
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.
Volume 12(1)
Pages 2136
Published 2021-4-9
DOI 10.1038/s41467-021-22402-x
PII 10.1038/s41467-021-22402-x
PMID 33837198
PMC PMC8035405
MeSH Animals Bone Resorption / drug therapy* Bone Resorption / pathology Cell Differentiation / drug effects Cell Differentiation / physiology Cell Line Disease Models, Animal Female Femur / cytology Femur / diagnostic imaging Femur / drug effects Femur / pathology Humans Male Mice Mice, Knockout Osteoblasts / drug effects Osteoblasts / metabolism Osteoclasts / drug effects Osteoclasts / metabolism Osteogenesis / drug effects Osteogenesis / physiology* Parathyroid Hormone / administration & dosage* Primary Cell Culture RNA-Seq Secretory Leukocyte Peptidase Inhibitor / genetics Secretory Leukocyte Peptidase Inhibitor / metabolism* Up-Regulation / drug effects X-Ray Microtomography
IF 12.121
DNA material CSII-EF-MCS (RDB04378)