硫酸乙酰肝素成骨作用及成骨机制的研究进展

Research progress in osteogenesis and osteogenic mechanism of heparan sulfate

目的对硫酸乙酰肝素(heparan sulfate,HS)在骨形成和骨重建方面的作用进行讨论,综述其成骨机制的最新研究进展。方法查阅国内外有关HS体外作用于成骨细胞系、HS和HS复合支架材料作用于骨缺损动物模型以及HS蛋白聚糖影响骨骼发育的研究文献,并进行综合分析。结果 HS长链通过非共价结合方式和参与骨折愈合的生长因子结合,尤其是肝素结合性生长因子(如FGFs、BMP、TGF-β)等,保护这些生长因子免受蛋白酶降解,并可直接参与生长因子信号转导和骨细胞功能调节。HS调控成骨作用机制主要包括:刺激干细胞向成骨细胞分化、提高成骨细胞分化能力、促进骨基质形成、维持骨基质稳定和加速骨基质矿化。结论 HS的成骨作用显著,随着对其安全性的不断探索完善,HS可能成为临床治疗骨缺损延迟愈合和不愈合的有效手段,并有望为骨组织工程技术提供更多选择。

Objective To discuss the role ofheparan sulfate （HS） in bone formation and bone remoaeung an, summarize the research progress in the osteogenic mechanism of HS. Methods The domestic and abroad related literature about HS acting on osteoblast cell line in vitro, HS and HS composite scaffold materials acting on the ani- mal bone defect models, and the effect of HS proteoglycans on bone development were summarized and analyzed. Results Many growth factors involved in fracture healing especially heparin-binding growth factors, such as fibroblast growth factors, bone morphogenetic protein, and transforming growth factor [3, are connected noncovalently with long HS chains. HS proteoglycans protect these proteins from protease degradation and are directly involved in the regulation of growth factors signaling and bone cell function. HS can promote the differentiation of stem cells into osteoblasts and enhance the differentiation of osteoblasts. In bone matrix, HS plays a significant role in promoting the formation, maintaining the stability, and accelerating the mineralization- Condusion The osteogenesis of HS is pronounced. HS is likely to become the clinical treatment measures of fracture nonunion or delayed union, and is expected to provide more choices for bone tissue engineering with identification of its long-term safety.