Neutrophil-derived catecholamines mediate negative stress effects on bone

Autor: Miriam E. A. Tschaffon-Müller, Elena Kempter, Lena Steppe, Sandra Kupfer, Melanie R. Kuhn, Florian Gebhard, Carlos Pankratz, Miriam Kalbitz, Konrad Schütze, Harald Gündel, Nele Kaleck, Gudrun Strauß, Jean Vacher, Hiroshi Ichinose, Katja Weimer, Anita Ignatius, Melanie Haffner-Luntzer, Stefan O. Reber
Jazyk: angličtina
Rok vydání: 2023
Předmět:
Zdroj: Nature Communications, Vol 14, Iss 1, Pp 1-15 (2023)
Druh dokumentu: article
ISSN: 2041-1723
DOI: 10.1038/s41467-023-38616-0
Popis: Abstract Mental traumatization is associated with long-bone growth retardation, osteoporosis and increased fracture risk. We revealed earlier that mental trauma disturbs cartilage-to-bone transition during bone growth and repair in mice. Trauma increased tyrosine hydroxylase-expressing neutrophils in bone marrow and fracture callus. Here we show that tyrosine hydroxylase expression in the fracture hematoma of patients correlates positively with acknowledged stress, depression, and pain scores as well as individual ratings of healing-impairment and pain-perception post-fracture. Moreover, mice lacking tyrosine hydroxylase in myeloid cells are protected from chronic psychosocial stress-induced disturbance of bone growth and healing. Chondrocyte-specific β2-adrenoceptor-deficient mice are also protected from stress-induced bone growth retardation. In summary, our preclinical data identify locally secreted catecholamines in concert with β2-adrenoceptor signalling in chondrocytes as mediators of negative stress effects on bone growth and repair. Given our clinical data, these mechanistic insights seem to be of strong translational relevance.
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