Neutrophil-derived catecholamines mediate negative stress effects on bone

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.

Chronic sensory contact with subordinated conspecifics promotes splenic glucocorticoid resistance in experimentally wounded C57BL/6N male mice

“…In line with own previous studies 16 , 30 , 31 , CSC mice of both the SHAM and i.p.-wounded group developed adrenal enlargement and thymus involution, which is the most predictive biomarker for classification and class prediction in the CSC paradigm 26 and a typical sign of chronic stress in rodents 16 , 32 – 35 . These findings convincingly indicate that the CSC paradigm worked reliably in the current study, independent of SHAM or i.p.…”

What’s New in Musculoskeletal Basic Science

“…Chronic mental stress is associated with growth retardation, osteoporosis, and fracture risk. Tschaffon-Müller et al 13 analyzed the effect of mental stress on bone healing clinically and in mice. In patients with ankle fracture, depression, psychosocial stress, and low social functioning were associated with an increased expression of tyrosine hydroxylase (TH) in fracture hematoma and delayed bone healing.…”