SLPI is a critical mediator that controls PTH-induced bone formation.
Animals
Bone Resorption
/ drug therapy
Cell Differentiation
/ drug effects
Cell Line
Disease Models, Animal
Female
Femur
/ cytology
Humans
Male
Mice
Mice, Knockout
Osteoblasts
/ drug effects
Osteoclasts
/ drug effects
Osteogenesis
/ drug effects
Parathyroid Hormone
/ administration & dosage
Primary Cell Culture
RNA-Seq
Secretory Leukocyte Peptidase Inhibitor
/ genetics
Up-Regulation
/ drug effects
X-Ray Microtomography
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
09 04 2021
09 04 2021
Historique:
received:
03
04
2020
accepted:
12
03
2021
entrez:
10
4
2021
pubmed:
11
4
2021
medline:
4
5
2021
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 33837198
doi: 10.1038/s41467-021-22402-x
pii: 10.1038/s41467-021-22402-x
pmc: PMC8035405
doi:
Substances chimiques
Parathyroid Hormone
0
Secretory Leukocyte Peptidase Inhibitor
0
Slpi protein, mouse
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
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