OIC-A006在体外和体内促进成骨.docVIP

  OIC-A006 在体外和体内促进成骨# 刘鹏程，蔡明** （同济大学附属第十人民医院骨科，上海 200027） 5 10 15 20 25 30 35 40 45 摘要：骨形态发生蛋白（BMPs）是一种强有力的成骨因子。然而必须考虑到 BMPs 的安全 性，效用性和性价比。如今，研究者投入了极大的兴趣去寻找一种能安全地促进骨形成，有 利于骨修复的化合物。根据以往大量筛选分析的结果，我们发现了一种强有力的成骨诱导化 合物，该胺素类化合物被命名为 OIC-A006。在本研究中，我们旨在探讨 OIC-A006 在体外 和体内对骨髓基质干细胞成骨诱导的影响。我们观察到不同浓度的 OIC-A006，特别是在最 佳浓度 6.25μM 时可以刺激骨髓基质干细胞表达碱性磷酸酶（ALP），核心结合因子 a1 （Cbfa1），骨桥蛋白（OPN）和骨钙素（OC），并在体外形成钙化结节。骨组织培养条件 下，OIC-A006 能刺激新生小鼠颅骨和跖骨形成新骨，表明 OIC-A006 能起到积极的成骨作 用。此外，为了阐明 OIC-A006 在体内成骨的潜力，我们使用了煅烧颗粒骨复合一定剂量的 OIC-A006 移植至临界骨缺损处来干预兔颅骨缺损模型。这些结果首次证实，OIC-A006 能在 体外和体内促进成骨。这种新的化合物可能会成为一个新的能促进骨折愈合和骨再生的生长 因子替代物。 关键词：骨诱导；骨修复；骨髓间充质干细胞；胺素 中图分类号：R681.8 OIC-A006 promotes osteogenesis in vitro and in vivo Liu Pengcheng, Cai Ming (Department of Orthopedics,Shanghai Tenth People’s Hospital, Tongji University, ShangHai 200027) Abstract: Bone morphogenesis proteins (BMPs) are one of the potent bone-forming factors. However, the safety, utility, and cost effectiveness of BMPs must be considered. Nowadays, there has been substantial interest in developing a chemical compound that safely promotes bone formation and facilitates fracture repair. Based on previous research with high throughout screening assay, we found one potent osteogenic inductive compound, named as OIC-A006 (Osteogenic inducible compound-active 006), which is classified in the amine family. In this study, we aimed to investigate the inducing effects of OIC-A006 on osteogenesis by bone marrow stem cells (BMSCs) in vitro and in vivo. We demonstrated that OIC-A006, at different concentrations, especially at optimal concentration of 6.25 μM, could stimulate BMSCs to express alkaline phosphatase (ALP), core-binding factor a1 (Cbfa1), osteopontin (OPN) and osteocalcin (OC), and to form calcified nodules in vitro. Under the bone tissue culture conditions, OIC-A006 also stimulated new bone formation of murine calvarial and metatarsal bone, indicating that OIC-A006 may exert positive effects on osteogenesis. Furthermore, to elucidate the in v