Beta-arrestin-2 and G-protein dependent signaling to stimulate fracture healing with parathyroid hormone

• Applicant: Professor Dr. Richard Stange, since 5/2016
• Subject Area: Orthopaedics, Traumatology, Reconstructive Surgery
• Term: from 2015 to 2019
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 272825466

Up to 10% of all fractures do not heal in a timely manner or lead to non-union. Currently there no clinically approved pharmacological agents are available to stimulate fracture healing systemically. Experimental and early clinical studies have shown that parathyroid hormone (PTH) possess osteoinductive properties. However, the mechanisms of action are poorly understood. Whereas intermittent treatment with PTH stimulates bone formation, continuous treatment leads to bone resorption. PTH exerts its biological actions through the PTH1-receptor. After ligand receptor interaction a G-protein and a beta arrestin-2 dependent pathway are induced. Experimental studies in osteoporosis have shown that selective stimulation of the beta-arrestin dependent pathway stimulates bone formation without stimulating bone resorption. The aim oft he current study is to analyze the effect of a selective stimulation oft he PTH1 receptor on fracture healing. The study will be performed in a closed fracture model in mice in vivo and in an osteoblastic cell culture in vitro. In vivo and in vitro the G-protein dependent pathway and the beta-arrestin dependent pathway will be stimulated selectively. Additionally, both pathways will be stimulated with normal PTH 1-34. The results oft he study could be crucial fort he development of new pharmacological agents for stimulation of fracture healing.

• DFG Programme: Research Grants
• Ehemaliger Antragsteller: Privatdozent Dr. Patric Garcia, until 4/2016