gms | German Medical Science

Deutscher Kongress für Orthopädie und Unfallchirurgie (DKOU 2019)

22. - 25.10.2019, Berlin

Adrenoceptor expression profile during progression of intervertebral disc degeneration

Meeting Abstract

  • presenting/speaker Johannes Kupka - Orthopedic University Hospital Friedrichsheim, Dr. Rolf M. Schwiete Research Unit for Osteoarthritis, Frankfurt am Main, Germany
  • Richard Bostelmann - Department of Neurosurgery, University Clinic Duesseldorf, Duesseldorf, Germany
  • Andrea Meurer - Orthopädische Universitätsklinik Friedrichsheim gGmbH, Orthopädie und Orthopädische Chirurgie, Frankfurt, Germany
  • Frank Zaucke - Orthopädische Uniklinik Friedrichsheim, Dr. Rolf M. Schwiete Forschungsbereich für Osteoarthrose, Frankfurt am Main, Germany
  • Marcus Rickert - Orthopedic University Hospital Friedrichsheim, Dr. Rolf M. Schwiete Research Unit for Osteoarthritis, Frankfurt am Main, Germany
  • Zsuzsa Jenei-Lanzl - Orthopädische Uniklinik Friedrichsheim, Dr. Rolf M. Schwiete Forschungsbereich für Osteoarthrose, Frankfurt am Main, Germany

Deutscher Kongress für Orthopädie und Unfallchirurgie (DKOU 2019). Berlin, 22.-25.10.2019. Düsseldorf: German Medical Science GMS Publishing House; 2019. DocAB41-1050

doi: 10.3205/19dkou331, urn:nbn:de:0183-19dkou3319

Veröffentlicht: 22. Oktober 2019

© 2019 Kupka 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: The etiology of IVD degeneration (IVDD) is multifactorial: age, gender, environmental factors, or mechanical loading are involved in the pathogenesis [1]. Recent studies revealed that norepinephrine (NE), a major neurotransmitter of the sympathetic nervous system, plays a role in the insufficient regeneration of articular cartilage tissue [2]. It is known that healthy and degenerating IVDs are innervated by sympathetic nerve fibers [3]. However, adrenoceptor (AR) expression in IVD tissue has never been analyzed systematically. The aim of this study was to investigate adrenoceptor expression in healthy versus degenerated IVD tissue.

Methods: Samples of degenerated human IVDs (n=43) were collected from patients undergoing spondylodesis. The degree of degeneration in anonymized samples was determined intraoperatively. Expression of all known AR subtypes was evaluated by PCR in IVD tissue homogenates and in isolated IVD cells. Furthermore, human IVD samples were stained immunohistochemically for AR proteins. Finally, AR expression was analyzed on spine sections of 10 months old wildtype (WT) and of a mouse line that develops early spontaneous disc degeneration (SM/J mice [4]). Dimethylmethylene blue staining was used to visualize proteoglycans and tissue structure.

Results and conclusion: In total human IVD homogenates α1A-, α1B-, α2A-, α2B-, α2C-, β1-, and β2ARs genes were expressed. The same expression pattern was found in isolated IVD cells after 14 days in culture. In human IVD sections only β2AR was detectable at the protein level and the signal was restricted to the outer and inner annulus fibrosus (AF) but not found in the nucleus pulposus (NP). Similarly, in IVDs of WT and SM/J mice only β2AR was detected in the inner and sometimes in the outer AF tissue. In WT spine sections, the β2AR signal was strong in the lateral zones of the AF and weaker towards the cartilaginous endplate. In contrast, in SM/J mice the signal intensity was markedly increased in zones adjacent to the endplate. α2aAR and α2cAR were not detectable in human or murine sections at the protein level.

For the first time, we demonstrate the existence of ARs, especially of β2AR, in IVD tissue. Its differential expression in healthy and degenerated IVD suggests that the sympathicus might play a role in IVDD. Further studies will address disease relevant mechanisms and thereby help to develop novel therapy options for IVDD.


References

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Martirosyan NL, Patel AA, Carotenuto A, Kalani MY, Belykh E, Walker CT, Preul MC, Theodore N. Genetic Alterations in Intervertebral Disc Disease. Front Surg. 2016 Nov 21;3:59.
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Grässel S, et al. The Sensory and Sympathetic Nervous System in Cartilage Physiology and Pathophysiology in Cartilage: Volume 2: Pathophysiology. Cham: Springer International Publishing; 2017. p. 191-227.
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Tomaszewski KA, Saganiak K, Gładysz T, Walocha JA. The biology behind the human intervertebral disc and its endplates. Folia Morphol (Warsz). 2015;74(2):157-68. DOI: 10.5603/FM.2015.0026 Externer Link
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