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，肝素硫酸酯蛋白聚糖家族，特别是syndecans，起着重要的作用。我们的研究结果表明，在没有任何刺激的情况下，Syndecan-4对体外成骨细胞和破骨细胞的发育没有明显的影响。然而，在白细胞介素-1 - β刺激下，只有Syndecan-4特异性表达。在骨折愈合过程中，Syndecan-4缺失的动物表现出愈合延迟，骨痂中软骨形成增强。我们的结果指出了成软骨细胞增殖的差异，以及细胞外基质重塑的改变。在胚胎骨发育过程中，Syndecan-2的代偿作用在出生后的愈合过程中失败。本项目将研究骨折愈合初期炎症阶段对Syndecan-2和-4表达的影响。因此，骨折后的炎症反应将被抑制，在Syndecan-4存在和不存在的情况下，将分析愈合情况。此外，我们将在体外研究Syndecan-4对早期成软骨细胞分化的影响。这是一个在初始炎症阶段之后立即开始的过程，对于正确的愈合过程至关重要。

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.