Varkey Mathew, Kucharski Cezary, Haque Takrima, Sebald Walter, Uludağ Hasan
Department of Chemical and Materials Engineering, Faculty of Engineering, University of Alberta, Edmonton, Alberta, Canada.
Clin Orthop Relat Res. 2006 Feb;443:113-23. doi: 10.1097/01.blo.0000200236.84189.87.
Basic fibroblast growth factor (bFGF) and bone morphogenetic protein-2 (BMP-2) are actively pursued for stimulation of bone formation. To assess their promise for systemic therapy of osteoporosis, we ascertained the effects of bFGF and BMP-2 on bone marrow cells in vitro. Bone marrow cells were obtained from young (8 weeks) and adult (32 weeks) rats by femoral aspiration and were exposed to osteogenic medium (ie, basal medium with 10 mM beta-glycerolphosphate and 100 nM dexamethasone) containing the growth factors. The cell viability in osteogenic medium was reduced after 3 weeks but not if the concentration of beta-glycerolphosphate/dexamethasone was reduced to 3 mM/30 nM. Unlike BMP-2, bFGF at 2-50 ng/mL was capable of enhancing long-term cell viability. Continuous treatment of bone marrow cells for 3 weeks resulted in dose-dependent stimulation of mineralization by BMP-2, but not by bFGF, whose activity was optimal at 2-10 ng/mL. To explore the effect of short-term exposure, bone marrow cells were treated with growth factors for 1 week and subsequent mineralization was investigated. BMP-2 exposure increased the extent of mineralization, but bFGF was not effective after the short exposure. We concluded bFGF was more potent (ie, required lower concentration) for stimulating osteogenic parameters, but BMP-2 effects were lasting on the bone marrow cells.
碱性成纤维细胞生长因子(bFGF)和骨形态发生蛋白-2(BMP-2)因能刺激骨形成而备受关注。为评估它们用于骨质疏松症全身治疗的前景,我们在体外确定了bFGF和BMP-2对骨髓细胞的影响。通过股骨穿刺从幼年(8周)和成年(32周)大鼠获取骨髓细胞,并将其暴露于含有生长因子的成骨培养基(即含有10 mMβ-甘油磷酸和100 nM地塞米松的基础培养基)中。3周后,成骨培养基中的细胞活力降低,但如果将β-甘油磷酸/地塞米松的浓度降至3 mM/30 nM则不会降低。与BMP-2不同,2 - 50 ng/mL的bFGF能够提高长期细胞活力。对骨髓细胞连续处理3周导致BMP-2对矿化有剂量依赖性刺激作用,而bFGF则没有,bFGF在2 - 10 ng/mL时活性最佳。为探究短期暴露的影响,用生长因子处理骨髓细胞1周,随后研究矿化情况。暴露于BMP-2增加了矿化程度,但短期暴露后bFGF无效。我们得出结论,bFGF在刺激成骨参数方面更有效(即所需浓度更低),但BMP-2对骨髓细胞的作用更持久。