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- Title
Neutrophil-derived catecholamines mediate negative stress effects on bone.
- Authors
Tschaffon-Müller, Miriam E. A.; Kempter, Elena; Steppe, Lena; Kupfer, Sandra; Kuhn, Melanie R.; Gebhard, Florian; Pankratz, Carlos; Kalbitz, Miriam; Schütze, Konrad; Gündel, Harald; Kaleck, Nele; Strauß, Gudrun; Vacher, Jean; Ichinose, Hiroshi; Weimer, Katja; Ignatius, Anita; Haffner-Luntzer, Melanie; Reber, Stefan O.
- 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. Authors present both preclinical data in mice and clinical data from humans in support of the hypothesis that stress negatively affects bone growth and repair. These effects are mediated by neutrophil-derived catecholamines inhibiting cartilage-to-bone transition via β2-adrenoceptor signaling in chondrocytes.
- Subjects
BONE growth; GROWTH disorders; FRACTURE healing; TYROSINE hydroxylase; CATECHOLAMINES; MYELOID cells; BONE mechanics; BONE regeneration
- Publication
Nature Communications, 2023, Vol 14, Issue 1, p1
- ISSN
2041-1723
- Publication type
Article
- DOI
10.1038/s41467-023-38616-0