DFG Collaborative Research Centre 1444
This Collaborative Research Centre aims to unravel the basic mechanisms that differentiate between success and failure in regeneration of musculoskeletal tissue using bone healing as a role model.
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Subproject 9 - Principal Investgators
CRC 1444, Spokesperson & Scientific Coordinator, Subprojects 8, 9, 13 & Central Administrative Project | RU 2165 Subproject 1
Mechano-dependency of early bone healing and angiogenesis
Mechano-dependency of early bone healing and angiogenesis will be the focus of Duda and Gerhardt. This project aims to understand how mechanical loading drives vascular proliferation and callus organisation during early bone healing in an age dependent manner. It will focus on key cell-cell interactions in early cell-matrix self-assembly and on forces exerted by either blood flow or extrinsic loading and their consequences for functional vascularisation and bone marrow reconstitution. Duda and Gerhardt hypothesise that core mechanisms of endothelial and pericyte organisation – more specifically YAP/TAZ signalling – are modulated in their mechano-sensitivity during early bone healing. They further hypothesise that YAP/TAZ signalling is affected by advanced age and leads to a lack of mechano-sensation in cells of aged individuals but may be rescued by extrinsic mechanical perturbations.
Directional Vascularisation and Bone Formation
Energy Supply & Consumption | Force Transmission & Sensing
The processes of bone healing proceed strictly from proximal to distal. This is reflected in cell displacement and migration, but also strongly in fibroblastic tissue formation and the accompanying vascularization as well as bone marrow reorganization. Subsequently, the build-up of newly mineralized tissue is also strictly directed.
In collaboration with subprojekt P10
Angiogenesis and extracellular matrix assembly in bone healing and bone growth
Energy Supply & Consumption | Force Transmission & Sensing
ECM deposition and micro-vascular self-assembly are key to successful healing. External mechanical stability and cellular mechano-transduction thereby control early hematoma remodeling, micro-vascular organization and ECM formation.
In collaboration with subprojekt P10
Dynamics of ECM and vascular system organization in early stages of bone healing
Inflammatory Response | Energy Supply & Consumption
Vessel formation aligns with structured collagen organization. The extracellular matrix of the fracture site actively guides the process of vascularization during bone healing. This alignment is orchestrated by the local presence of adaptive immune cells and disappears in the local presence of more experienced adaptive immune cells.
In collaboration with subprojekt P14
Mechanocrines – YAP/TAZ dependent endothelial paracrine signaling
Energy Supply & Consumption | Force Transmission & Sensing
Mechanically induced paracrine signals – Mechanocrines - released from endothelial cells regulate cellular behaviour of surrounding cells like pericytes and fibroblasts.
In collaboration with subprojekt P10
Water binding properties regulate tissue mechanics and enable MRI detection of biophysical alterations
Energy Supply & Consumption | Force Transmission & Sensing
Mechanical properties of the ECM are key characteristics of cell niches. Our data illustrate that the proportion of loosely to strongly bound water is a distinctive ECM property that regulates its mechanics and they suggest a crucial role of PGs for elastic and viscous characteristics.
In collaboration with subprojekt P10
Team
Investigates the dynamics of the ECM and vascular system during bone healing at the cellular level
Examines crosstalk of endothelial cells and pericytes in vitro and on-a-chip with a focus on mechano-transducers YAP and TAZ
Studies the mechanical and osmotic properties of the extracellular matrix
Explores interplay of angiogenesis and ECM assembly during bone healing and bone growth.
In vivo mechanical stimulation and bone adaptation as well as healing dynamics
