B6 N: Effects of psychosocial trauma on bone homeostasis and fracture healing
PI: M. Haffner-Luntzer, S. Reber
Stress-related mental disorders, including post-traumatic stress disorder (PTSD), have been associated with osteoporosis and increased fracture risk, although the underlying mechanisms are currently not fully understood. PTSD is a stress-related pathology characterized by hypocorticism and sympathetic nervous- system activation. Importantly, β-adrenergic receptor (β-AR) signaling locally in the bone is known to affect bone mass, fracture healing, and chondrocyte differentiation and to promote myelopoiesis. In agreement with these findings, we recently demonstrated that cartilage-to-bone transition during endochondral ossification is disturbed in mice exposed to the chronic subordinate colony housing (CSC) paradigm, a preclinically-validated model of PTSD characterized by systemic activation of the sympathetic nervous system, promotion of bone-marrow myelopoiesis, immune activation and basal hypocorticism. Furthermore, tyrosine hydroxylase (TH), the rate-limiting enzyme in the synthesis of catecholamines, was strongly increased following CSC locally in myeloid bone marrow cells, suggesting that on-site secreted catecholamines might be involved in mediating CSC effects on endochondral ossification. Our preliminary data further suggest compromised fracture healing in CSC mice, paralleled by a dysregulated immune response and the appearance of TH-positive cells in the early fracture hematoma.
Based on these findings, the aim of the proposed project is to investigate the cellular and molecular mechanisms underlying the effects of chronic psychosocial traumatization on bone homeostasis and regeneration. Using specific transgenic mouse models and pharmacological approaches, we will study the hypotheses that PTSD-induced local catecholamine production disturbs endochondral bone formation by activation of β-AR-related signaling specifically in chondrocytes during bone homeostasis and regeneration.
Melanie Haffner-Luntzer, Ph.D.
Institut für Unfallchirurgische Forschung und Biomechanik
Tel.: +49 731 500 55324
Prof. Dr. rer. nat. Stefan Reber
Klinik für psychosomatische Medizin und Psychotherapie, Sektion für molekulare Psychosomatik Albert-Einstein-Allee 23
Tel.: +49 731 500 61943