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

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，硫酸乙酰肝素蛋白多糖家族，尤其是Syndecans，起着重要的作用。我们的结果表明，在没有任何刺激的情况下，Syndecan-4对体外培养的成骨细胞或破骨细胞的发育没有明显影响。然而，只有Syndecan-4的表达在IL-1β刺激下被特异性地诱导。在骨折愈合过程中，Syndecan-4缺陷动物表现出愈合延迟，骨痂中软骨形成增强。我们的结果指出了软骨母细胞增殖的差异，但也指出了细胞外基质重塑的变化。Syndecan-2的代偿作用，在胚胎骨骼发育过程中显示出来，但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-4表达的影响。因此，在Syndecan-4存在和不存在的情况下，骨折后的炎症反应将被抑制，愈合情况将被分析。此外，将在体外研究Syndecan-4对早期软骨细胞分化的影响。这是一个在发炎阶段之后立即开始的过程，对于正确的愈合过程是必不可少的。

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.