Basic fibroblast growth factor induces osteoclast formation in murine bone marrow cultures

Area of Science:

• Bone Biology and Physiology
• Cellular and Molecular Biology
• Endocrinology

Background:

• Basic fibroblast growth factor (bFGF) is implicated in various cellular processes, including bone metabolism.
• Osteoclast-like cells (OCLs) are crucial for bone resorption, and their formation is tightly regulated.

Purpose of the Study:

• To investigate the effect of bFGF on osteoclast-like cell formation in mouse bone marrow cultures.
• To elucidate the role of prostaglandin E2 (PGE2) in bFGF-induced osteoclastogenesis.

Main Methods:

• Bone marrow cells from C57BL/6 mice were cultured for 7 days with varying concentrations of bFGF or 1,25(OH)2 vitamin D3.
• OCL formation was quantified, and characterized by multinucleation, tartrate-resistant acid phosphatase (TRAP) positivity, calcitonin receptor expression, and resorption pit formation.
• PGE2 levels were measured, and the effect of prostaglandin synthesis inhibitors (indomethacin, NS-398) on bFGF-induced OCL formation was assessed.

Main Results:

• bFGF dose-dependently increased OCL formation, with effects comparable to 1,25(OH)2D3 at higher concentrations.
• bFGF enhanced OCL formation when added during early proliferative (days 1-2) and differentiating (days 3-4) phases, but not late phases (days 5-6).
• bFGF significantly increased PGE2 production, and indomethacin or NS-398 completely blocked bFGF-induced OCL formation.

Conclusions:

• bFGF stimulates osteoclast-like cell formation in mouse bone marrow cultures.
• The mechanism involves the requirement of prostaglandin synthesis, suggesting a critical role for PGE2 in bFGF-mediated osteoclastogenesis.
• This pathway is a significant contributor to bFGF-stimulated bone resorption.