title: Interleukin-7 is a direct inhibitor of in vitro osteoclastogenesis.
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.
authors.affiliation: Department of Medicine, The University of Connecticut Health Center, Farmington, Connecticut 06030, USA. slee@neuron.uchc.edu
authors.forename: Sun-Kyeong
authors.initials: SK
authors.lastname: Lee
authors.forename: Judith F
authors.initials: JF
authors.lastname: Kalinowski
authors.forename: Sandra L
authors.initials: SL
authors.lastname: Jastrzebski
authors.forename: Lynn
authors.initials: L
authors.lastname: Puddington
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Lorenzo
mesh_terms: D000135:Acid Phosphatase / Q000032:analysis; D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology; D001854:Bone Marrow Cells / Q000166:cytology; D002352:Carrier Proteins / Q000494:pharmacology; D002452:Cell Count; D002454:Cell Differentiation; D002478:Cells, Cultured; D002762:Cholecalciferol / Q000494:pharmacology; D003114:Colony-Forming Units Assay; D003433:Crosses, Genetic; D005434:Flow Cytometry; D006098:Granulocytes; D015851:Interleukin-7 / Q000172:deficiency / Q000494:pharmacology* / Q000502:physiology; D007527:Isoenzymes / Q000032:analysis; D016173:Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D008264:Macrophages; D008562:Membrane Glycoproteins / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010010:Osteoclasts / Q000166:cytology*; D010281:Parathyroid Hormone / Q000494:pharmacology; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; D000071681:Tartrate-Resistant Acid Phosphatase
chemical_list: D002352:Carrier Proteins; D015851:Interleukin-7; D007527:Isoenzymes; D008562:Membrane Glycoproteins; D010281:Parathyroid Hormone; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; C505687:Tnfrsf11a protein, mouse; C505689:Tnfsf11 protein, mouse; D002762:Cholecalciferol; D016173:Macrophage Colony-Stimulating Factor; D000135:Acid Phosphatase; D000071681:Tartrate-Resistant Acid Phosphatase