Neutrophil-derived catecholamines mediate negative stress effects on bone.

Area of Science:

• Orthopedics
• Neuroscience
• Endocrinology

Background:

• Mental traumatization is linked to impaired bone growth, osteoporosis, and increased fracture risk.
• Previous research indicated that mental trauma disrupts the cartilage-to-bone transition crucial for bone development and repair.

Purpose of the Study:

• To investigate the molecular mechanisms linking mental stress to impaired bone growth and fracture healing.
• To explore the role of tyrosine hydroxylase and catecholamines in mediating the negative effects of stress on bone.

Main Methods:

• Correlation analysis of tyrosine hydroxylase expression in fracture hematoma with patient-reported stress, depression, and pain scores.
• Assessment of bone growth and healing in mice lacking tyrosine hydroxylase in myeloid cells under chronic psychosocial stress.
• Evaluation of bone growth in chondrocyte-specific β2-adrenoceptor-deficient mice subjected to stress.

Main Results:

• Tyrosine hydroxylase expression in human fracture hematomas positively correlated with stress, depression, pain, and impaired healing perception.
• Mice lacking myeloid tyrosine hydroxylase were protected from stress-induced bone growth and healing disturbances.
• Mice with chondrocyte-specific β2-adrenoceptor deficiency were also protected from stress-induced bone growth retardation.

Conclusions:

• Locally secreted catecholamines, acting via β2-adrenoceptor signaling in chondrocytes, mediate the detrimental effects of stress on bone growth and repair.
• These findings highlight a significant translational relevance for understanding and potentially treating stress-related bone pathologies.