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

• Applicant: Professor Dr. Richard Stange
• Subject Area: Orthopaedics, Traumatology, Reconstructive Surgery
• Term: from 2010 to 2014
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 181474177

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.

• DFG Programme: Research Grants
• Participating Persons: Professorin Dr. Jessica Bertrand; Privatdozentin Dr. Rita Dreier; Professor Dr. Thomas Pap