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

Nat Commun. 2021 Apr 9;12(1):2136. doi: 10.1038/s41467-021-22402-x.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 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


  • Parathyroid Hormone
  • Secretory Leukocyte Peptidase Inhibitor
  • Slpi protein, mouse