Project Details
Projekt
The role of the heparansulfate proteoglycan syndecan-1 in bone metabolism
Applicant
Professor Dr. Richard Stange
Subject Area
Orthopaedics, Traumatology, Reconstructive Surgery
Term
from 2014 to 2019
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 259129953
The transmembrane heparansulphate proteoglycan syndecan-1 acts as a mediator of signals between the cell and its environment. Especially under stress conditions, the presence of syndecan proteins represents a significant survival advantage. Syndecans act as co-receptor for growth factors or signaling molecules, as mediator for binding extracellular matrix molecules and influence cell adhesion or formation of cytoskeleton which is important in cell migration. Syndecan-1 is expressed in mesenchymal cells of the bone marrow while bone formation and even during fracture healing. Several studies postulate the role of syndecan-1 in recruitment of cells to regions of tissue damage (e.g. injury) or mediation of cell-cell-contacts for adhesion or transmigration (e.g. leukocytes). Absence of syndecan-1 leads to decreased trabecular bone structures of lumbar spine and tibia in young mice (4 month). Additionally, syndecan-1 deficient mice show less biomechanical strength of the bone. Initial studies of primary osteoblasts (sdc1-/-. vs. wild type) showed yet that this decreased bone formation is not caused by an altered osteoblast differentiation or mineralization. But it was shown that die communication between osteoblasts and osteoclasts within the osteoclastogenesis was impaired. In our project we want to characterize the function of syndecan-1 during osteoclast differentiation using co-cultures of osteoblast- and osteoclast precursor cells that may shed light on differences in the communication of these cell types due to syndecan-1 deficiency, which may be important for bone formation and organization in vivo. To charakterize the function of syndecan-1 in bone homoestasis during development we will analyse histologically the bone structure of mice at different ages (embryo, neonatal to 18 month) and the cell composition of the bone marrow compartment. Furthermore, in a second part of the project, using a mouse fracture model we want to investigate a possible function of syndecan-1 in inflammatory processes like fracture healing. The healing progression will be characterized with particular focus on the enchondral ossification process. This part will be supported by cell culture experiments using bone cells stimulated with important growth factors and cytokines which will than be characterized for their function with and lacking syndecan-1. Our result will provide important insights in the great variety of functions of the syndecan protein family at the interface between the cell and its environment during bone healing.
DFG Programme
Research Grants
