Project Details
Projekt
Analysis of early immune responses and the role of mast cells in fracture healing
Subject Area
Immunology
Rheumatology
Rheumatology
Term
from 2013 to 2017
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 237502027
The immune system is known to play a crucial role in fracture healing, as the bone repair process starts with a local inflammatory response. The early immune response after fracture is regarded to be essential for subsequent bone regeneration by initiating down-stream responses leading to tissue repair; however, the knowledge about the impact of certain immune cells is scarce so far. Mast cells are potent pro-inflammatory sensors of the innate immune system. Their role in bone metabolism has been discussed since a long time, as systemic mastocytosis is connected with a decreased bone mass. The function of mast cells in fracture healing and bone regeneration, however, has not been investigated so far. Few studies indicated that mast cells might be present during the inflammatory phase and at later stages of bone healing. Therefore, this project aims to characterize the early inflammatory phase of fracture healing and specifically the impact of mast cells during the time course of bone regeneration. We will use a newly generated Cre/lox-based mouse model of constitutive mast cell deficiency (Mcpt5-Cre R-DTA), in which cell numbers of other immune cells are not affected. Fracture healing will be investigated in these mice using a standardized osteotomy of the femur, which is stabilized with an external fixator, in comparison to their mast cell competent Cre negative littermate controls. Extensive analysis during the time course of fracture healing will answer the questions, whether mast cells modulate the early immune response, and whether mast cells specifically influence vascularization and bone formation in the fracture callus at later stages. The expected results will considerably contribute to the understanding of the interaction of the immune system and bone regeneration.
DFG Programme
Priority Programmes
Subproject of
SPP 1468:
Osteoimmunology - IMMUNOBONE - A Programme to Unravel the Mutual Interactions between the Immune System and Bone
Participating Person
Professor Dr. Michael Amling
