Interleukin-33 is expressed in differentiated osteoblasts and blocks osteoclast formation from bone marrow precursor cells

Autor: Andrew N. J. McKenzie, André Gessner, Alexander S. Spiro, Tim N. Hissnauer, Mario M. Zaiss, Thorsten Schinke, Thomas Streichert, Thomas Bickert, Kristofer Wintges, Joachim Albers, Georg Schett, F. Timo Beil, Michael Amling, Andrea Kristina Horst, Kristin Klaetschke, Johannes Keller, Jochen Schulze
Rok vydání: 2010
Předmět:
medicine.medical_specialty
Endocrinology
Diabetes and Metabolism
Osteoimmunology
Acid Phosphatase
Gene Expression
Osteoclasts
Bone Marrow Cells
Cell Count
Bone resorption
Bone and Bones
Bone remodeling
Mice
Calcitriol
Osteoclast
Internal medicine
Cell Line
Tumor
Bone cell
medicine
Animals
Orthopedics and Sports Medicine
Bone Resorption
Cells
Cultured
Mice
Knockout
Osteoblasts
biology
Chemistry
Tartrate-Resistant Acid Phosphatase
Interleukins
Macrophage Colony-Stimulating Factor
Macrophages
RANK Ligand
Granulocyte-Macrophage Colony-Stimulating Factor
Osteoblast
Cell Differentiation
Receptors
Interleukin
Interleukin-33
Interleukin-1 Receptor-Like 1 Protein
Cell biology
Basophils
Eosinophils
Isoenzymes
Mice
Inbred C57BL
medicine.anatomical_structure
Endocrinology
RANKL
biology.protein
Bone marrow
Stromal Cells
Zdroj: Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research. 26(4)
ISSN: 1523-4681
Popis: Since the hematopoetic system is located within the bone marrow, it is not surprising that recent evidence has demonstrated the existence of molecular interactions between bone and immune cells. While interleukin 1 (IL-1) and IL-18, two cytokines of the IL-1 family, have been shown to regulate differentiation and activity of bone cells, the role of IL-33, another IL-1 family member, has not been addressed yet. Since we observed that the expression of IL-33 increases during osteoblast differentiation, we analyzed its possible influence on bone formation and observed that IL-33 did not affect matrix mineralization but enhanced the expression of Tnfsf11, the gene encoding RANKL. This finding led us to analyze the skeletal phenotype of Il1rl1-deficient mice, which lack the IL-33 receptor ST2. Unexpectedly, these mice displayed normal bone formation but increased bone resorption, thereby resulting in low trabecular bone mass. Since this finding suggested a negative influence of IL-33 on osteoclastogenesis, we next analyzed osteoclast differentiation from bone marrow precursor cells and observed that IL-33 completely abolished the generation of TRACP+ multinucleated osteoclasts, even in the presence of RANKL and macrophage colony-stimulating factor (M-CSF). Although our molecular studies revealed that IL-33 treatment of bone marrow cells caused a shift toward other hematopoetic lineages, we further observed a direct negative influence of IL-33 on the osteoclastogenic differentiation of RAW264.7 macrophages, where IL-33 repressed the expression of Nfatc1, which encodes one of the key transciption factors of osteoclast differentiation. Taken together, these findings have uncovered a previously unknown function of IL-33 as an inhibitor of bone resorption. © 2011 American Society for Bone and Mineral Research.
Databáze: OpenAIRE
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