Effect of basic fibroblast growth factor on the growth and differentiation of adult stromal bone marrow cells: Enhanced development of mineralized bone-like tissue in culture

Abstract

Rat stromal bone marrow cells (SBMC) were shown to produce mineralized bone-like tissue in culture in the presence of dexamethasone, ascorbic acid, and beta-glycerophosphate. The addition of 3 ng/ml of basic fibroblast growth factor (bFGF) resulted in a significant increase in formation of mineralized tissue. The present study was aimed at assessing the effect of bFGF on the proliferation and differentiation of SBMC and on the sequential development of mineralized bone-like tissue in culture. Transmission electron microscopy of bFGF-treated cultures demonstrated the development of a multilayered structure resembling mineralized bone tissue consisting of cell layers embedded within a heavy extracellular matrix. The matrix was rich in bundles of collagen fibers associated with extensive mineral deposits consisting of hydroxyapatite as determined by infrared spectrophotometry. The addition of 3 ng/ml of bFGF resulted in significant enhancement of [3H]thymidine and [3H]proline incorporation and protein accumulation by 12-, 2.5-, and 2.5-fold, respectively. bFGF treatment increased cAMP responsiveness, alkaline phosphatase activity, osteocalcin level, 45Ca2+ deposition, and mineralized-like tissue formation and induced the earlier expression of these markers in the treated culture. A biphasic sequence of events was observed during the development of mineralized bone-like tissue in bFGF-treated and control cultures. The first phase is characterized by cell proliferation and matrix accumulation and is reflected by a progressive increase in [3H]thymidine and [3H]proline incorporation until day 11. The second phase, which follows, is characterized by a sharp decline in cell proliferation and matrix accumulation and a concomitant expression of osteoblast differentiation as reflected by the progressive increase in alkaline phosphatase activity, mineral deposition, and osteocalcin expression. Treatment of cultures with bFGF accentuated this biphasic sequence of events. These results indicate that bFGF has the capacity to stimulate both the growth and the biochemical functions of SBMC obtained from a young adult animal.

Periodontal regeneration following application of basic fibroblast growth factor-2 in combination with beta tricalcium phosphate in class III furcation defects in dogs

“…We attempted to determine the optimal dose of bFGF-2 for periodontal regeneration in dogs from several previous reports. bFGF-2 had a dose-dependent effect on periodontal regeneration at a dose ranging from 0 to 0.16% per implant [3][4][5][6][7][8][9][10][11][12][13][14][15][26][27][28][29] . Hayashi et al reported that new bone formation was smaller in the 0.56% bFGF-2 (100 µg bFGF-2/3×3×2 mm gelatin hydrogel) implant compared to the 0.056% bFGF-2 (10 µg bFGF-2/3×3×2 mm gelatin hydrogel) implant; however, there were no significant differences between them 29) .…”

“…New bone formation in the F group was observed along the mesial space onto the distal rootsurface and the distal space onto the mesial root-surface and the new bone had a dimple in the center. It has been reported that the concentration of bFGF-2 regulates the cell proliferation of osteoblasts in vitro 3,30,31) . The present results suggested that bFGF-2 applied on the decalcified dentin surface may promote proliferation and differentiation of osteoblasts near the root surface.…”

“…Basic fibroblast growth factor-2 (bFGF-2) is a heparinbinding growth factor that exhibits potent angiogenic activity and mitogenic ability in mesenchymal cells [1][2][3][4][5][6][7] and periodontal ligament cells [8][9][10][11] . Several studies have reported that bFGF-2 induces potent periodontal tissue regeneration along with new alveolar bone and cementum formation without aberrant healing such as root resorption and ankylosis in critical size defects of animal models [12][13][14] .…”

The Lamina Propria of Adult Human Oral Mucosa Harbors a Novel Stem Cell Population

“…Osteogenic, chondrogenic, and adipocytic lineages represented the mesodermal germ layer. Nodular mineralized deposits characteristic to human osteoblastic cultures derived from bone marrow stromal progenitor cells [30,41] were identified with Alizarin Red S staining in 5 weeks old cultures as described elsewhere [41] (Fig. 3A).…”

Concentration- and time-dependent response of human gingival fibroblasts to fibroblast growth factor 2 immobilized on titanium dental implants

“…23 FGF2 can be immobilized on Ti surfaces pretreated with oxygen plasma, 24 and the TiO 2 nanotubular surface benefits drug control release 25 and immobilization of other growth factors such as, bone morphogenetic protein 2 as well.…”