Stimulatory effects of fibroblast growth facor-2 on bone formation and bone resorption

骨骼领域中最大的需求之一是刺激骨骼形成的生物活性剂。我们以前曾报道过纤维块生长因子-2（FGF-2），一种适合于中等细胞的潜在突变体，并在不同的细胞类型中展示了对骨骼形成的强有力的无核反应。在一个临床应用中，我们在这里报告了一个单一的本地应用，即重组的人类FGF-2展示了一个在非人类primates的分形模型中的强骨活性。还有4分10只动物被单独处理在一个非工会状态甚至10周后，骨骼联盟在6周内完成了所有10只动物被处理在FGF-2。FGF-2在切割部位明显增加了骨骼质量和强度，因此提议成为一种生物骨骼代谢剂用于临床用途。在添加，对风湿性关节炎（RA）关节的合成流体的影响，对关节破坏的不同程度的影响 ... More 我被测试过了。具有大量联合破坏性和明显刺激的骨质疏松细胞形成的RA患者的协同流体和来自预标签的文化新生儿小鼠Calvariae的RA患者的合成流体，与具有轻度联合破坏性和骨质疏松症（OA）患者的RA患者的合成流体进行比较。在骨骼还原细胞因子中; FGF-2、肿瘤坏死因子A、白细胞介素A、IL-6和可溶性IL-6受体，只有FGF-2在合成流体中的融合与Larsen的等级积极相关，和一些RA患者显示出明显高于轻度RA患者的FGF-2融合。在一个共同培养系统中，骨胶原发生症被严重RA患者的合成流体刺激，被明显地抑制了对FGF-2的中性化抗体的抑制，而这种抑制比抗体对其他细胞因子的抑制更强。我们将包括在内分泌FGF-2生产中增加的合成流体可能会在诱导骨胶原发生过程中扮演RA患者的联合破坏的角色。Less（低）

One of the greatest needs in the bone field is a bioactive agent to stimulate bone formation. We previously reported that fibroblast growth factor-2 (FGF-2), a potent mitogen for a variety of mesenchymal cells, exhibited strong anabolic actions on bone formation in models of rodents and dogs. Aiming at a clinical application, here we report that a single local application of recombinant human FGF-2 exhibits strong osteogenic action in a fracture model of non-human primates. Although 4 out 10 animals treated with the vehicle alone remained in a nonunion state even after 10 weeks, bone union was complete at 6 weeks in all 10 animals treated with FGF-2. FGF-2 significantly increased bone mass and strength at the fracture site, and is therefore proposed to be an epochal bone anabolic agent for clinical use.In addition, the effect of the synovial fluid from knee joints of rheumatoid arthritis (RA) patient with different severities of joint destruction on osteoclastogenesis and bone resorpti … More on was examined. The synovial fluid of RA patients with severe joint destruction significantly stimulated osteoclastic cell formation and ィイD145ィエD1Ca release from prelabelled cultured neonatal mouse calvariae, compared to those of RA patients with mild joint destruction and osteoarthritis (OA) patients. Among bone resorptive cytokines; FGF-2, tumor necrosis factor-a, interleukin-a, IL-6, and soluble IL-6 receptor, only FGF-2 concentration in the synovial fluid was positively correlated to Larsen's grade, and severe RA patients showed significantly higher FGF-2 concentrations than mild RA patients. Osteoclastogenesis in a co-culture system which was stimulated by the synovial fluid of severe RA patients was significantly inhibited by a neutralizing antibody against FGF-2 and this inhibition was stronger than antibodies against other cytokines. We conclude that the increase in endogenous FGF-2 production in the synovial fluid may play a role in the joint destruction of RA patients by inducing osteoclastogenesis. Less