Project Details
Projekt
FOR 793: Mechanisms of Fracture Healing and Regeneration in Osteoporotic Bone
Subject Area
Medicine
Term
from 2007 to 2015
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 27463524
Osteoporosis is a metabolic bone disease caused by an imbalance of biological factors, which are important for the regulation of bone homeostasis. Important risk factors for the development of osteoporosis are genetic factors, the beginning menopause of women, progressive age and lack of activity. Osteoporosis leads to a strong reduction of bone mass and an impairment of bone architecture. The mechanical properties of the bone decrease. Consecutively, the risk of fractures increases. Every second woman and every fifth man over the age of 50 suffer on an osteoporotic fracture. The fractures occur mostly in the spine but also in the proximal femur, the radius and other localisations.
The treatment of osteoporotic fractures is difficult as bone healing is disturbed or delayed. The fixation of stabilising implants in the porous osteoporotic bone is difficult. Many studies reveal that patients with osteoporotic fractures often need long-term care. Therefore, it is of great importance to improve the treatment of osteoporotic fractures and to investigate the reasons for the delayed healing and regeneration in osteoporotic bone.
The aim of the Research Unit is to investigate the possible role of key factors in bone regeneration, which are important for the regulation of bone homeostasis. Such key factors might be central regulators of bone formation (leptin, ß-adrenergic signalling pathways), hormones (e.g. estrogens), dysfunction of stem cells (e.g. proliferation and differentiation capability), dysfunction of osteoblast activity (e.g. Wnt/LRP5/ß-Catenin signalling pathway) or osteoclast activity (e.g. receptor activator of NFkB (RANK/RANK)-ligand-system) and mechanical stimuli. Fracture healing studies with defined osteoporotic animal models and cell culture studies will be performed to gain basic knowledge about the disturbed regeneration capacity of osteoporotic bone. This will be the basis for the development of new strategies for the treatment of osteoporotic fractures.
The treatment of osteoporotic fractures is difficult as bone healing is disturbed or delayed. The fixation of stabilising implants in the porous osteoporotic bone is difficult. Many studies reveal that patients with osteoporotic fractures often need long-term care. Therefore, it is of great importance to improve the treatment of osteoporotic fractures and to investigate the reasons for the delayed healing and regeneration in osteoporotic bone.
The aim of the Research Unit is to investigate the possible role of key factors in bone regeneration, which are important for the regulation of bone homeostasis. Such key factors might be central regulators of bone formation (leptin, ß-adrenergic signalling pathways), hormones (e.g. estrogens), dysfunction of stem cells (e.g. proliferation and differentiation capability), dysfunction of osteoblast activity (e.g. Wnt/LRP5/ß-Catenin signalling pathway) or osteoclast activity (e.g. receptor activator of NFkB (RANK/RANK)-ligand-system) and mechanical stimuli. Fracture healing studies with defined osteoporotic animal models and cell culture studies will be performed to gain basic knowledge about the disturbed regeneration capacity of osteoporotic bone. This will be the basis for the development of new strategies for the treatment of osteoporotic fractures.
DFG Programme
Research Units
Projects
- Differentielle Genexpression und putative therapeutische Gene für die Heilung der osteoporotischen Fraktur in Mesenchymalen Stammzellen (Applicant Jakob, Franz )
- Entwicklung und biomechanische Charakterisierung diaphysärer und metaphysärer Frakturheilungsmodelle im Klein- und Großtier. (Applicant Claes, Lutz )
- Entwicklung und Charakterisierung eines Osteoporose-Großtiermodells mit Diskonnektion von Hypothalamus und Hypophyse (HPD-Schaf) (Applicant Amling, Michael )
- Mechanismen der Frakturheilung und Knochenregeneration bei Osteoporose (Applicant Amling, Michael )
- Molekulare Charakterisierung der Störungen zellulärer Mechanotransduktion bei Osteoporose (Applicants Ignatius, Anita ; Jakob, Franz )
- Regulation der Knochenformation und Knochenmasse durch Wnt-abhängige Signaltransduktion (Applicant Schinke, Ph.D., Thorsten )
- Untersuchung der Frakturheilung bei Hypochlorhydrie-induzierter Osteoporose in Maus und Schwein (Applicants Amling, Michael ; Ignatius, Anita ; Jakob, Franz ; Mutschler, Wolf )
- Untersuchung der Frakturheilung in osteoporotischen Tiermodellen: Einfluss der Störung der zentralen Regulation der Knochenformation und der Wnt-abhängigen Signaltransduktion (Applicant Ignatius, Anita )
- Überexpression des Receptor Activator of NF-KB Liganden (RANKL) zur Untersuchung der metaphysären Frakturheilung im osteoporotischen Großtiermodell (Applicants Schieker, Matthias ; Wolf, Eckhard )
Spokesperson
Professor Dr. Michael Amling
