gms | German Medical Science

Deutscher Kongress für Orthopädie und Unfallchirurgie (DKOU 2018)

23.10. - 26.10.2018, Berlin

Tryptophan hydroxylase 2: a potential marker for bone mass regulation

Meeting Abstract

  • presenting/speaker Diaa Eldin S. Daghma - Justus-Liebig University of Giessen, Institute for experimentel trauma Surgery, Giessen, Germany
  • Michael Bader - 4Max Delbrück Center for Molecular Medicine, Berlin, Germany
  • Polina Peeva - Max Delbrück Center for Molecular Medicine, Berlin, Germany
  • Natalia Alenina - Max Delbrück Center for Molecular Medicine, Berlin, Germany
  • Marian Kampschulte - Klinik für Diagnostische und Interventionelle , Giessen, Germany
  • Jan Belikom - Klinik für Diagnostische und Interventionelle , Giessen, Germany
  • Thaqif El Khassawna - Justus-Liebig University of Giessen, Institute for experimentel trauma Surgery, Giessen, Germany
  • Christian Heiss - Justus-Liebig University of Giessen, Institute for experimentel trauma Surgery, Giessen, Germany

Deutscher Kongress für Orthopädie und Unfallchirurgie (DKOU 2018). Berlin, 23.-26.10.2018. Düsseldorf: German Medical Science GMS Publishing House; 2018. DocGF21-1311

doi: 10.3205/18dkou530, urn:nbn:de:0183-18dkou5301

Veröffentlicht: 6. November 2018

© 2018 Daghma et al.
Dieser Artikel ist ein Open-Access-Artikel und steht unter den Lizenzbedingungen der Creative Commons Attribution 4.0 License (Namensnennung). Lizenz-Angaben siehe http://creativecommons.org/licenses/by/4.0/.


Gliederung

Text

Objectives: Age related bone loss results from dysregulated bone metabolism. Aging is associated to further disorders related to central serotonin. Serotonin influence bone remodeling based on the origin of synthesis. However, understanding the effect of central serotonin loss on bone metabolism in relation to aging requires a longitudinal and detailed analysis. Therefore, young and old knockout rat model deprived from Tryptophan hydroxylase 2 (Tph2-/-) to inhibit the synthesis of serotonin in brain were used and compared with wild type counter parts. Such understanding might suggest the use of serotonin as therapeutic or prophylactic agent for age related bone loss.

Methods: Forty wild Type (WT), and forty Tph2-/- rats were euthanized at (W = Weeks) 6W, 20W, 30W, and 40W. Time points were chosen to study bone parameters before and after the age of peak bone mass in rats. Femora were collected for radiological testing using microcomputer tomography analysis to assess bone quality. The samples were then used for histomorphometrical analysis of matrix mineralization by means of Von Kossa / van Gieson stain. Osteoblasts and osteoclasts were examined using immunostainings.

Results and conclusion: Bone Mineral Density (BMD) and Tissue Mineral Density (TMD) in the WT increased towards from 6W to 30W. However, no significant difference between 30 and 40W was seen. Although the BMD and TMD increased in Tph2-/- rats from 6W to 30W, both BMD and TMD dropped significantly at 40W of age. Von Kossa/ Van Gieson stain differentiates mineralized and non-mineralized bone matrix portions. Interestingly, lower mineralized bone matrix and higher non-mineralized bone matrix portions were seen in Tph2-/- rats at 40W compared with 30W. Intriguingly, both osteoblasts and osteoclasts area and number increased exponentially with age in Tph2-/- rats from 6W until 40W, whereas the WT showed a fluctuating pattern in osteoblast and osteoclast activity between time points. Further, WT showed more osteoclast at 20W and 40W when compared with Tph2-/- rats.

Discussion: Understanding the regulation of bone mass is important to treat systemic skeletal diseases. The loss of Tph2-/-, indicated better bone parameters when compared with the WT. Nonetheless, the discrepancies at the later time points suggest a more rapid age-related bone loss. The current results suggest a therapeutic potential of TPH2 to regulate age-related bone loss. However, dysregulation in bone matrix mineralization requires further analysis. Therefore, ultrastructural analysis of fiber arrangement and properties, investigation of extracellular matrix proteins and osteocyte morphological changes are under investigation.