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Isolation of Mesenchymal Stem Cells from Human Alveolar Periosteum and Effects of Vitamin D on Osteogenic Activity of Periosteum-derived Cells
Published on: May 4, 2018
Basic fibroblast growth factor inhibits osteoclast formation induced by 1alpha,25-dihydroxyvitamin D(3) through
1Research Institute of Life Science, Snow Brand Milk Products Co. Ltd. , Tochigi, 329-0512, Japan.
Abstract:
Basic fibroblast growth factor (bFGF) inhibited osteoclast-like cell (OCL) formation in cocultures of mouse spleen cells with either osteoblasts or a stromal cell line, ST2, in the presence of 1alpha, 25-dihydroxyvitamin D(3) [1,25(OH)(2)D(3)]. bFGF directly acted on osteoblasts/stromal cells, but not osteoclast progenitors, to inhibit 1,25(OH)(2)D(3)-induced OCL formation. bFGF suppressed the mRNA expression of osteoclast differentiation factor (ODF) but did not affect that of osteoclastogenesis inhibitory factor (OCIF) in ST2 cells treated with 1,25(OH)(2)D(3) and dexamethasone. Enzyme-linked immunosorbent assay showed that bFGF hardly affected OCIF production in the treated ST2 cells. A genetically engineered soluble form of ODF, but not anti-OCIF neutralizing antibody, abolished bFGF-mediated inhibition of OCL formation. bFGF suppressed the binding of (125)I-labeled OCIF to both ST2 cells and osteoblasts treated with 1,25(OH)(2)D(3). These findings indicate that bFGF inhibits 1,25(OH)(2)D(3)-induced OCL formation via suppression of ODF production by osteoblasts/stromal cells.
Insights
Basic fibroblast growth factor (bFGF) inhibits osteoclast formation by reducing osteoclast differentiation factor (ODF) in bone cells. This finding reveals a new mechanism for regulating bone resorption.
Area of Science:
- Cell Biology
- Bone Biology
- Endocrinology
Background:
- Osteoclast-like cell (OCL) formation is crucial for bone remodeling.
- 1alpha, 25-dihydroxyvitamin D(3) [1,25(OH)(2)D(3)] is a key inducer of OCL formation.
- Basic fibroblast growth factor (bFGF) is a signaling molecule with diverse cellular effects.
Purpose of the Study:
- To investigate the effect of bFGF on OCL formation.
- To elucidate the mechanism by which bFGF influences OCL differentiation.
- To determine the role of osteoclast differentiation factor (ODF) and osteoclastogenesis inhibitory factor (OCIF) in bFGF-mediated inhibition.
Main Methods:
- Coculture of mouse spleen cells with osteoblasts or ST2 stromal cells.
- Treatment with 1,25(OH)(2)D(3), dexamethasone, and bFGF.
- Measurement of OCL formation.
- Analysis of ODF and OCIF mRNA expression using RT-PCR.
- Enzyme-linked immunosorbent assay (ELISA) for OCIF production.
- Functional assays using soluble ODF and anti-OCIF antibodies.
- Binding assays for OCIF.
Main Results:
- bFGF inhibited 1,25(OH)(2)D(3)-induced OCL formation.
- bFGF acted directly on osteoblasts/stromal cells, not osteoclast progenitors.
- bFGF suppressed ODF mRNA expression but did not affect OCIF mRNA or production.
- Soluble ODF, but not anti-OCIF antibody, abolished bFGF's inhibitory effect.
- bFGF reduced the binding of OCIF to osteoblasts and ST2 cells.
Conclusions:
- bFGF inhibits 1,25(OH)(2)D(3)-induced OCL formation.
- The mechanism involves the suppression of ODF production by osteoblasts/stromal cells.
- bFGF's action is independent of OCIF production and binding.
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