Project Details
Projekt
Sympathetic influences on articular cartilage regeneration capacity and osteoarthritis manifestation
Applicant
Dr. Zsuzsa Jenei-Lanzl
Subject Area
Orthopaedics, Traumatology, Reconstructive Surgery
Term
from 2016 to 2021
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 277277765
Osteoarthritis (OA) pathogenesis involves the interaction of articular cartilage with surrounding tissues, which are innervated by the sympathicus. In earlier studies, we detected the sympathetic neurotransmitter and stress hormone norepinephrine (NE) in the synovial fluid of trauma and OA patients and observed the inhibition of chondrogenesis in bone marrow mesenchymal stem cell culture. Recently, we confirmed the anti-chondrogenic effect of NE in synovial adipose stem cells, which was mediated by α2a-adrenoceptor-dependent ERK1/2 phosphorylation. Furthermore, we demonstrated for the first time that DMM surgery-induced experimental OA in mice resulted in an elevated sympathetic tone. Moreover, sympathectomy led to less cartilage degradation but accelerated OA-characteristic cartilage calcification and subchondral bone thickening compared to WT mice. In the second funding period, the sympathetic-parasympathetic balance of OA patients and its correlations with clinical OA symptoms and cellular responses of different joint tissues will be analyzed. In addition, the effect of experimental chronic stress on OA progression in the murine DMM model will be investigated. These experiments will unravel the role of chronic stress in OA pathogenesis and might help to develop novel therapeutic options targeting the sympathicus.
DFG Programme
Research Units
