Syndecan-4 as a regulator of chondroblast development during fracture healing

Syndecan-4 作为骨折愈合过程中成软骨细胞发育的调节剂

• 批准号: 181474177
• 负责人: Professor Dr. Richard Stange
• 金额: --
• 依托单位: Institut für Muskuloskelettale Medizin
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2010
• 资助国家: 德国
• 起止时间: 2009-12-31 至 2013-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/181474177?language=en
• 关键词: Syndecan; regulator; chondroblast; development; during

The development and healing of bone depends on a complex interplay of cells and extracellular matrix together with an exchange of cytokines and growth factors. Thereby, the family of heparansulfate proteoglycans, especially the syndecans, play an important role. Our results revealed that without any stimulus Syndecan-4 has no considerably influence on the development of osteoblasts or osteoclasts in vitro. However, only the expression of Syndecan-4 was specifically induced upon stimulation with interleukin-1beta. During fracture healing, Syndecan-4 deficient animals show a delayed healing with enhanced cartilage formation in the callus. Our results point to differences in the proliferation of chondroblasts but also alterations in remodeling of the extracellular matrix. Compensatory effects of Syndecan-2, as were shown during embryonic bone development fail at postnatal healing processes. In the present project the influence of the initial inflammation phase of fracture healing on Syndecan-2 and -4 expression will be investigated. Therefore, the inflammatory reaction after fracture will be repressed and healing will be analyzed in presence and absence of Syndecan-4. Furthermore, the influence of Syndecan-4 on the early chondroblast differentiation will be investigated in vitro. This is a process starting immediately after the initiate inflammation phase and being essential for a correct healing process.

骨的发育和愈合依赖于细胞和细胞外基质的复杂相互作用以及细胞因子和生长因子的交换。因此，硫酸乙酰肝素蛋白聚糖家族，特别是多配体蛋白聚糖，发挥着重要作用。结果表明，在无任何刺激的情况下，Syndecan-4对体外培养的成骨细胞和破骨细胞的发育没有明显影响。然而，只有Syndecan-4的表达是特异性诱导后，刺激白细胞介素-1 β。在骨折愈合期间，Syndecan-4缺陷动物显示愈合延迟，骨痂中软骨形成增强。我们的研究结果指出，在成软骨细胞的增殖差异，但也在细胞外基质重塑的改变。Syndecan-2的补偿作用，如在胚胎骨发育过程中所示，在出生后愈合过程中失败。在本项目中，将研究骨折愈合的初始炎症阶段对Syndecan-2和Syndecan-4表达的影响。因此，骨折后的炎症反应将被抑制，并且将在存在和不存在Syndecan-4的情况下分析愈合。此外，将在体外研究Syndecan-4对早期成软骨细胞分化的影响。这是一个过程开始后立即启动炎症阶段，是一个正确的愈合过程必不可少的。