gms | German Medical Science

German Congress of Orthopaedics and Traumatology (DKOU 2019)

22. - 25.10.2019, Berlin

Sensory nervous system impact on cartilage and subchondral bone pathology in a murine OA model

Meeting Abstract

  • presenting/speaker Dominique Muschter - Orthopädische Klinik der Universität Regensburg, Experimentelle Orthopädie, ZMB im Biopark I, Regensburg, Germany
  • Shahed Taheri - University Medical Center Goettingen, Orthopedic Surgery and Plastic Surgery, Department for Trauma Surgery, Göttingen, Germany
  • Lutz Fleischhauer - Munich University of Applied Science, Department of Applied Natural Sciences and Mechatronics, Munich, Germany
  • Tanja Späth - Orthopädische Klinik der Universität Regensburg, Experimentelle Orthopädie, ZMB im Biopark I, Regensburg, Germany
  • Hauke Clausen-Schaumann - Munich University of Applied Science, Department of Applied Natural Sciences and Mechatronics, Munich, Germany
  • Arndt F. Schilling - Universitätsmedizin Göttingen, Klinik für Unfallchirurgie, Orthopädie und plast. Chirurgie, Göttingen, Germany
  • Susanne Grässel - Orthopädische Klinik der Universität Regensburg, Experimentelle Orthopädie, ZMB im BioPark 1, Regensburg, Germany

Deutscher Kongress für Orthopädie und Unfallchirurgie (DKOU 2019). Berlin, 22.-25.10.2019. Düsseldorf: German Medical Science GMS Publishing House; 2019. DocAB22-360

doi: 10.3205/19dkou101, urn:nbn:de:0183-19dkou1018

Published: October 22, 2019

© 2019 Muschter 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: Alterations in sensory nerve fiber distribution might contribute to the ongoing degenerative processes in osteoarthritis (OA). Sensory neuropeptides like substance P(SP) and alpha calcitonin-gene-related peptide(αCGRP) are able to affect bone cell metabolism. SP effects on bone can be either catabolic or anabolic, whereas αCGRP effects are primarily anabolic. How sensory neuropeptides are involved in OA pathology is not well understood. Here, we aim to analyze the influence of an altered sensory neuropeptide microenvironment on subchondral bone and cartilage changes in a murine OA model.

Methods: OA was induced in wildtype (WT), SP-knockout (Tachykinin1 (Tac)1-/-) and αCGRP-knockout mice by surgical destabilization of the medial meniscus (DMM). Medial subchondral bone structure was analyzed using µCT and ultrahigh-resolution nanoCT technique. Cartilage alterations were evaluated in SafraninO-stained sections of knee joints according to OARSI guidelines and by stiffness analysis using atomic force microscopy (AFM).

Results and conclusion: OARSI scores confirmed significant cartilage degradation in all DMM groups after 12 weeks. AFM analysis 2 weeks after DMM surgery showed an increased cartilage stiffness of WT and αCGRP-/- mice in all cartilage zones compared to respective Sham mice. Superficial zone cartilage of Sham Tac1-/- mice revealed substantially higher stiffness compared to WT and αCGRP-/- Sham mice. DMM surgery induced significant softening of the superficial layer in Tac1-/- mice, whereas stiffness of the middle zone cartilage was critically increased compared to Sham. 2 weeks after DMM surgery, higher bone volume density (BV/TV) and lower specific bone surface (BS/BV) of subchondral bone from Tac1-/- mice indicated early sclerotic changes compared to Sham mice. WT mice had reduced BV/TV and elevated BS/BV compared to αCGRP-/- and Tac1-/- mice after 12 weeks, independent from OA induction. NanoCT analysis of subchondral bone 8 weeks after surgery demonstrated a thicker layer of calcified cartilage in the medial tibia of all DMM groups, as well as a significant increase in medial condyle diameter compared to respective Sham mice. DMM surgery induced meniscal ossification in all groups, with significantly stronger effects in the neuropeptide k.o. mice. Additionally 8 weeks after DMM surgery, subchondral osteoclast numbers in αCGRP-/- mice were significantly elevated compared to WT mice. By trend, neuropeptide k.o. mice displayed higher subchondral osteoclast numbers per BS compared to WT mice, unrelated to OA induction.

SP-deficient mice revealed a cartilage phenotype that might contribute to the considerable cartilage alterations early after induction of murine OA, ultimately leading to subchondral bone sclerosis at the early stage. In general, loss of sensory neuropeptides induced subchondral bone sclerosis in conjunction with advanced aging and not OA. Underlying mechanisms remain elusive but changes in bone cell composition might contribute to this bone phenotype.