Regulation of osteoblast differentiation:: A novel function for fibroblast growth factor 8
Regulation of osteoblast differentiation:: A novel function for fibroblast growth factor 8
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DOI：
10.1210/en.2005-1502
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发表时间：
2006-05-01
期刊：
影响因子：
4.8
通讯作者：
Härkönen, PL
中科院分区：
文献类型：
--
作者：
Valta, MP;Hentunen, T;Härkönen, PL
成纤维细胞生长因子（FGF）家族的几个成员在骨骼组织的发育中具有重要作用。FGF-8在发育中的骨骼中广泛表达，但其功能仍不清楚。在这项研究中，我们询问FGF-8是否可以在间充质干细胞向成骨细胞谱系的分化中发挥作用。如果在成骨细胞分化的早期阶段将FGF-8添加到培养物中，则将FGF-8添加到小鼠骨髓培养物中有效地增加初始细胞增殖以及随后的成骨细胞特异性碱性磷酸酶产生、骨结节形成和钙积累。外源性FGF-8也刺激MG 63骨肉瘤细胞的增殖，其被FGF-8b的中和抗体阻断。此外，以非常高的水平表达和分泌FGF-8的Shionogi 115（S115）小鼠乳腺癌细胞的肝素结合生长因子级分在骨髓培养物中具有与外源性FGF-8类似的效果。有趣的是，S115细胞的实验性裸鼠肿瘤呈现异位骨和软骨形成，如典型的组织学和软骨特异性标志物（II型和IX型胶原）和骨（骨钙素）的表达所证明的。这些结果表明，FGF-8有效地预先决定骨髓细胞分化为成骨细胞，并在体外增加骨形成。FGF-8也可能在体内刺激骨形成。结果表明，FGF-8，这是由很大比例的恶性乳腺癌和前列腺肿瘤表达，除其他因素外，也可能参与骨转移瘤的形成。
Several members of the fibroblast growth factor (FGF) family have an important role in the development of skeletal tissues. FGF-8 is widely expressed in the developing skeleton, but its function there has remained unknown. We asked in this study whether FGF-8 could have a role in the differentiation of mesenchymal stem cells to an osteoblastic lineage. Addition of FGF-8 to mouse bone marrow cultures effectively increased initial cell proliferation as well as subsequent osteoblast-specific alkaline phosphatase production, bone nodule formation, and calcium accumulation if it was added to the cultures at an early stage of osteoblastic differentiation. Exogenous FGF-8 also stimulated the proliferation of MG63 osteosarcoma cells, which was blocked by a neutralizing antibody to FGF-8b. In addition, the heparin-binding growth factor fraction of Shionogi 115 (S115) mouse breast cancer cells, which express and secrete FGF-8 at a very high level, had an effect in bone marrow cultures similar to that of exogenous FGF-8. Interestingly, experimental nude mouse tumors of S115 cells present ectopic bone and cartilage formation as demonstrated by typical histology and expression of markers specific for cartilage (type II and IX collagen) and bone (osteocalcin). These results demonstrate that FGF-8 effectively predetermines bone marrow cells to differentiate to osteoblasts and increases bone formation in vitro. It is possible that FGF-8 also stimulates bone formation in vivo. The results suggest that FGF-8, which is expressed by a great proportion of malignant breast and prostate tumors, may, among other factors, also be involved in the formation of osteosclerotic bone metastases.