BASIC FIBROBLAST GROWTH-FACTOR INDUCES OSTEOCLAST FORMATION IN MURINEBONE-MARROW CULTURES

We determined the effect of basic fibroblast growth factor (bFGF) on o steoclast-like cell (OCL) formation in bone marrow cultures using C57B L/6 mice, Cells were cultured for 7 days with or without bFGF at vario us concentrations or 10(-8) mol/L 1,25(OH)(2) vitamin D-3 [1,25(OH)(2) D-3]. bFGF dose-dependently increased OCL formation per well (10(-10) mol/L = 40 +/- 2; 10(-9) mol/L = 146 +/- 13; 10(-8) mol/L = 156 +/- 12 ) compared with control (<7 per well), The effects of bFGF at 10(-9) a nd 10(-8) mol/L were similar to that of 10(-8) mol/L 1,25(OH)(2)D-3 (1 54 +/- 11 per well), OCLs formed by bFGF were multinuclear, tartrate-r esistant acid phosphatase (TRAP)-positive, expressed calcitonin recept ors, and formed characteristic resorption pits, We also determined whe ther bFGF enhanced OCL formation during the early proliferative or lat e differentiating phases of the cultures, When bFGF (10(-8) mol/L) was added only on days 1-2 or days 3-4 of 6 day cultures, there was a sig nificant increase in OCL formation, In contrast, when bFGF was added o nly on days 5-6 few OCLs formed, Addition of bFGF at days 1-6 or days 1-2 and days 5-6 caused similar increases in OCL formation, which were greater than OCL formation induced by treatment for days 1-2 or days 1-4, We examined the production of prostaglandin E-2 (PGE,) in the cul tures because bFGF is a potent stimulator of PGE, synthesis in bone, a nd PGE, stimulates OCL formation, bFGF treatment significantly increas ed PGE, levels in 7 day cultures (controls = 1.4 +/- 0.1 nmol/L, 10(-8 ) mol/L bFGF = 132.5 +/- 0.7 nmol/L), In addition, treatment of marrow cultures with the prostaglandin synthesis inhibitors, indomethacin or NS-398 (both at 10(-6) mol/L), completely blocked bFGF-induced OCL fo rmation, We conclude that bFGF stimulates OCL formation in C57BL/6 bon e marrow cultures by mechanisms that require prostaglandin synthesis, This pathway is likely to be one mechanism by which bFGF stimulates re sorption. (C) 1998 by Elsevier Science Inc. All rights reserved.