Basic fibroblast growth factor inhibits osteoclast-like cell formation
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Published on: March 18, 2019
1Department of Biochemistry, Faculty of Dentistry, Kyushu University, Fukuoka, Japan.
Abstract:
Basic fibroblast growth factor (bFGF) inhibited osteoclast-like cell formation in co-cultures of mouse bone marrow cells either with the mouse stromal cell line, ST2, or with primary osteoblastic cells. Basic FGF significantly inhibited the osteoclast-like cell formation, induced by 1 alpha,25-dihydroxyvitamin D3[1 alpha, 25(OH)2D3] when the cytokine was added to the culture, at an intermediate stage, suggesting that bFGF inhibits the differentiation of the osteoclast progenitors. With regard to target cells, bFGF directly affected ST2; it increased [3H] thymidine uptake and decreased the number of alkaline phosphatase-positive cells. In contrast, bFGF had no inhibitory effect on the colony formation of bone marrow cells induced by macrophage colony stimulating factor in methylcellulose culture. In addition, ST2 cells treated with bFGF produced similar amounts of colony forming activity to those without the cytokine. These findings indicated that the bFGF is not involved in the proliferation of progenitor cells even in the presence of ST2 cells. Furthermore, bFGF inhibited osteoclast-like cell formation induced not only by 1 alpha,25(OH)2D3, but also by prostaglandin E2 and by interleukin-11. These results suggest that bFGF inhibits the common site of osteoclast-like cell formation, as induced by different mechanisms. Our data also indicated that the target cells for bFGF in inhibiting osteoclast formation are not osteoclast progenitors but stromal cells such as ST2 and osteoblastic cells, which support osteoclast development.
Insights
Basic fibroblast growth factor (bFGF) inhibits osteoclast formation by targeting stromal cells, not osteoclast progenitors. This finding reveals a key mechanism in bone remodeling regulation.
Area of Science:
- Cell Biology
- Biochemistry
- Osteology
Background:
- Osteoclast formation is crucial for bone remodeling.
- Stromal cells and osteoblastic cells play a supportive role in osteoclast development.
- Basic fibroblast growth factor (bFGF) is a cytokine with known roles in cell growth and differentiation.
Purpose of the Study:
- To investigate the role of bFGF in osteoclast-like cell formation.
- To identify the specific cellular targets of bFGF's inhibitory effects on osteoclastogenesis.
- To elucidate the mechanism by which bFGF influences osteoclast differentiation.
Main Methods:
- Co-culture of mouse bone marrow cells with ST2 stromal cells or primary osteoblastic cells.
- Induction of osteoclast-like cell formation using 1 alpha,25-dihydroxyvitamin D3, prostaglandin E2, and interleukin-11.
- Assessment of [3H] thymidine uptake and alkaline phosphatase activity in ST2 cells.
- Methylcellulose culture to evaluate progenitor cell proliferation.
Main Results:
- bFGF significantly inhibited osteoclast-like cell formation induced by various factors.
- bFGF treatment increased [3H] thymidine uptake and decreased alkaline phosphatase-positive cells in ST2 cells.
- bFGF did not affect progenitor cell proliferation or colony formation induced by macrophage colony stimulating factor.
- bFGF's inhibitory effect on osteoclast formation appears to target stromal/osteoblastic cells, not osteoclast progenitors.
Conclusions:
- bFGF inhibits osteoclast-like cell formation by acting on stromal cells (e.g., ST2) and osteoblastic cells.
- The mechanism involves inhibiting the differentiation of osteoclast progenitors rather than affecting progenitor proliferation.
- bFGF targets a common pathway in osteoclast formation irrespective of the inducing agent.
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