gms | German Medical Science

German Congress of Orthopedic and Trauma Surgery (DKOU 2017)

24.10. - 27.10.2017, Berlin

Chronic psychosocial stress disturbs the immune response and endochondral ossification after fracture

Meeting Abstract

  • presenting/speaker Melanie Haffner-Luntzer - Institute of Orthopedic Research and Biomechanics, University of Ulm, Ulm, Germany
  • Sandra Förtsch - Laboratory for Molecular Psychosomatics, University Medical Centre Ulm, Ulm, Germany
  • Verena Fischer - Institute of Orthopedic Research and Biomechanics, University of Ulm, Ulm, Germany
  • Katja Prystaz - Institute of Orthopedic Research and Biomechanics, University of Ulm, Ulm, Germany
  • Anna Kovtun - Institute of Orthopedic Research and Biomechanics, University of Ulm, Ulm, Germany
  • Yvonne Hägele - Institute of Orthopedic Research and Biomechanics, University of Ulm, Ulm, Germany
  • Anita Ignatius - Institute of Orthopedic Research and Biomechanics, University of Ulm, Ulm, Germany
  • Stefan O. Reber - Laboratory for Molecular Psychosomatics, University Medical Centre Ulm, Ulm, Germany

Deutscher Kongress für Orthopädie und Unfallchirurgie (DKOU 2017). Berlin, 24.-27.10.2017. Düsseldorf: German Medical Science GMS Publishing House; 2017. DocGR14-143

doi: 10.3205/17dkou497, urn:nbn:de:0183-17dkou4973

Published: October 23, 2017

© 2017 Haffner-Luntzer et al.
This is an Open Access article distributed under the terms of the Creative Commons Attribution 4.0 License. See license information at http://creativecommons.org/licenses/by/4.0/.


Outline

Text

Objectives: Stress is known to disturb bone homeostasis [Calarge 2014] and to promote systemic immune activation, as confirmed by both clinical and experimental studies [Langgartner 2015; Rohleder 2014]. Previous studies demonstrated that a balanced inflammatory response after fracture is crucial for successful bone healing [Kemmler 2015; Kovtun 2016]. Therefore, we hypothesize that chronic stress alters the inflammatory response after fracture, thus, leading to disturbed bone healing. Since chronic psychosocial stress represents the type of stressors mostly faced by humans [Goswami 2013], the aim of this study was to investigate the influence of chronic subordinate colony housing, a model for murine chronic psychosocial stress [Reber 2007] on fracture healing and the posttraumatic inflammatory response.

Methods: 7-weeks-old male C57BL/6 mice were subjected to chronic subordinate colony housing (CSC) for 19 days [Reber 2007]. CSC mice were housed in groups of four together with a dominant CD1 male mouse in order to induce chronic subordination. Single-housed (SHC) mice were used as controls. On day 20, a standardized femur osteotomy was applied, stabilized by an external fixator. Recruitment of immune cells to the site of fracture was assessed by fluorescence-activated cell sorting of the hematoma, 24h after fracture. Cytokine plasma levels were evaluated by multiplex analysis 24h and 21d after fracture. Fracture healing was analyzed by histomorphometry, 3-point-bending test and µCT analysis on days 10 and 21 after fracture. n=8/group. Student's t-test, p<0.05.

Results: Mice subjected to CSC displayed significantly increased numbers of neutrophils in the fracture hematoma (2.7% of living cells (SHC) vs. 4.8% (CSC)), whereas T- and B-lymphocytes were significantly reduced (T-lymphocytes: 1.4% of living cells (SHC) vs. 0.4% (CSC); B-lymphocytes: 1.2% (SHC) vs. 0.9% (CSC)). Ten days after surgery, callus tissue composition was similar between the groups. However, 21 days after fracture, CSC mice showed significantly decreased bending stiffness (1269 Nmm2 (SHC) vs. 855 Nmm2 (CSC)) and mineralization in the fracture callus (298 mgHA/mm3 (SHC) vs. 264 mgHA/mm3 (CSC)). Persisting cartilage was present in the callus of CSC mice, indicating disturbed endochondral ossification. Furthermore, interleukin-13 (IL-13) plasma concentration was significantly reduced in CSC vs. SHC mice at day 21 after fracture, whereas other cytokines were similar between the groups 24h and 21d after fracture.

Conclusion: Chronic psychosocial stress promotes the innate inflammatory response after fracture, while cells of the adaptive immune system were less present in the fracture hematoma, overall resulting in a misbalanced immune response after fracture. Furthermore, endochondral ossification was disturbed, which might be due to reduced levels of the T-helper cytokine IL-13, known to induce matrix metalloproteinase-mediated cartilage degradation [Nabbe 2015].