Regulation of Osteoclast Differentiation by Fibroblast Growth Factor 2: Stimulation of Receptor Activator of Nuclear Factor κB Ligand/Osteoclast Differentiation Factor Expression in Osteoblasts and Inhibition of Macrophage Colony-Stimulating Factor Functi

Autor: Toru Ogasawara, Takashi Shimoaka, Mika Katagiri, Daichi Chikazu, Kozo Nakamura, Tsuyoshi Takato, Hiroshi Kawaguchi, Naoshi Ogata
Rok vydání: 2001
Předmět:
musculoskeletal diseases
Macrophage colony-stimulating factor
medicine.medical_specialty
Endocrinology
Diabetes and Metabolism
Basic fibroblast growth factor
Gene Expression
Osteoclasts
Receptors
Cytoplasmic and Nuclear
Biology
Fibroblast growth factor
Receptors
Tumor Necrosis Factor
Cell Line
Mice
chemistry.chemical_compound
Osteoprotegerin
Osteoclast
Internal medicine
medicine
Animals
Orthopedics and Sports Medicine
RNA
Messenger
Receptor
Fibroblast Growth Factor
Type 1
Glycoproteins
Membrane Glycoproteins
Osteoblasts
Receptor Activator of Nuclear Factor-kappa B
Macrophage Colony-Stimulating Factor
Stem Cells
RANK Ligand
Receptor Protein-Tyrosine Kinases
Cell Differentiation
Osteoblast
Receptors
Fibroblast Growth Factor
Cell biology
Isoenzymes
medicine.anatomical_structure
Endocrinology
chemistry
Cyclooxygenase 2
Prostaglandin-Endoperoxide Synthases
RANKL
biology.protein
Fibroblast Growth Factor 2
Bone Remodeling
Carrier Proteins
Zdroj: Journal of Bone and Mineral Research. 16:2074-2081
ISSN: 0884-0431
DOI: 10.1359/jbmr.2001.16.11.2074
Popis: This study investigated the mechanism of direct and indirect actions of fibroblast growth factor 2 (FGF-2) on osteoclast differentiation using two mouse cell culture systems. In the coculture system of osteoblasts and bone marrow cells, FGF-2 stimulated osteoclast formation. This effect was decreased markedly by osteoprotegerin (OPG) or NS-398, a selective cyclo-oxygenase 2 (COX-2) inhibitor. FGF-2 (> or = 10(-9) M) stimulated receptor activator of nuclear factor kappaB ligand/osteoclast differentiation factor (RANKL/ODF) messenger RNA (mRNA) expression from 2 h to 7 days in cultured osteoblasts. NS-398 did not affect the early induction but decreased the later one, indicating that the later effect is mediated by COX-2 induction in osteoblasts. To study the direct action of FGF-2 on osteoclast precursors, we used mouse macrophage-like cell line C7 cells that can differentiate into osteoclasts in the presence of soluble RANKL/ODF (sRANKL/ODF) and macrophage colony-stimulating factor (M-CSF). Although osteoblasts expressed all FGF receptors (FGFR-1 to -4), only FGFR-1 was detected in C7 cells at various differentiation stages. FGF-2 alone or in combination with sRANKL/ODF did not induce osteoclastogenesis from C7 cells; however, FGF-2 from lower concentrations (> or = 10(-11) M) significantly decreased osteoclast formation induced by M-CSF in the presence of sRANKL/ODF. FGF-2 did not alter mRNA levels of M-CSF receptor (Fms) or RANK in C7 cells. Immunoprecipitation/ immunoblotting analyses revealed that tyrosine phosphorylation of several cellular proteins including Fms in C7 cells induced by M-CSF was inhibited by FGF-2 in the presence of sRANKL/ODF. We conclude that FGF-2 regulates osteoclast differentiation through two different mechanisms: (1) an indirect stimulatory action via osteoblasts to induce RANKL/ODF partly through COX-2 induction and prostaglandin production and (2) a direct inhibitory action on osteoclast precursors by counteracting M-CSF signaling.
Databáze: OpenAIRE
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