Interleukin-7 Is a Direct Inhibitor of in Vitro Osteoclastogenesis

Endocrinology. 2003 Aug;144(8):3524-31. doi: 10.1210/en.2002-221057.

Abstract

We examined the direct effects of IL-7 on osteoclastogenesis in murine bone marrow cultures, using cells from wild-type and IL-7- and IL-7 receptor (IL-7R)-deficient mice. IL-7 inhibited osteoclast-like cells (OCL) formation in macrophage colony-stimulating factor (M-CSF) and receptor activator of nuclear factor kappaB ligand (RANKL)-stimulated (both at 30 ng/ml) murine bone marrow cultures. Significant inhibitory effects were seen at 1 ng/ml (57%) and 10 ng/ml (86%). IL-7 also inhibited (P < 0.05) OCL formation in bone marrow cultures that were stimulated with vitamin D(3) (10(-8) M, 60%), bovine PTH (bPTH) (100 ng/ml, 54%), or RANKL alone (30 ng/ml, 50%). IL-7 (10 ng/ml) increased expression of the B lymphocyte marker B220 from 40-86% of total nonadherent cells in cultures treated with M-CSF and RANKL. Bone marrow cells from IL-7-deficient [IL-7 knockout (KO)] mice showed a significant (P < 0.05) increase in tartrate-resistant acid phosphatase(+) OCL numbers in cultures that were stimulated with vitamin D(3) (136 +/- 13.3%), bPTH (196 +/- 18.8%), or M-CSF and RANKL (160 +/- 7.2%). In contrast, in vitro osteoclast formation in bone marrow from IL-7R-deficient (IL-7R KO) mice showed a significant decrease in tartrate-resistant acid phosphatase(+) OCL numbers in cultures that were stimulated with vitamin D(3), PTH, RANKL, or M-CSF and RANKL. These results demonstrate that there are differences in the mechanisms regulating OCL formation between IL-7 KO and IL-7R KO cells. It seems that IL-7 is a direct inhibitor of OCL formation in vitro, based on results of adding IL-7 to wild-type cultures and the responses of IL-7 KO cells. It is unknown why IL-7R KO cells behave differently from IL-7 KO cells in vitro. However, it is possible that additional cytokines interact with IL-7R and that loss of these signals contributes to the responses of IL-7R KO cells. Alternatively, IL-7 may interact with multiple receptors.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Acid Phosphatase / analysis
  • Animals
  • B-Lymphocytes / cytology
  • Bone Marrow Cells / cytology
  • Carrier Proteins / pharmacology
  • Cell Count
  • Cell Differentiation*
  • Cells, Cultured
  • Cholecalciferol / pharmacology
  • Colony-Forming Units Assay
  • Crosses, Genetic
  • Flow Cytometry
  • Granulocytes
  • Interleukin-7 / deficiency
  • Interleukin-7 / pharmacology*
  • Interleukin-7 / physiology
  • Isoenzymes / analysis
  • Macrophage Colony-Stimulating Factor / pharmacology
  • Macrophages
  • Membrane Glycoproteins / pharmacology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Osteoclasts / cytology*
  • Parathyroid Hormone / pharmacology
  • RANK Ligand
  • Receptor Activator of Nuclear Factor-kappa B
  • Tartrate-Resistant Acid Phosphatase

Substances

  • Carrier Proteins
  • Interleukin-7
  • Isoenzymes
  • Membrane Glycoproteins
  • Parathyroid Hormone
  • RANK Ligand
  • Receptor Activator of Nuclear Factor-kappa B
  • Tnfrsf11a protein, mouse
  • Tnfsf11 protein, mouse
  • Cholecalciferol
  • Macrophage Colony-Stimulating Factor
  • Acid Phosphatase
  • Tartrate-Resistant Acid Phosphatase