OA-Model

Osteoarthritis (OA) is one of the leading causes of disability worldwide. In contrast with acute diseases like cancer, OA can adversely affect people’s quality of life over decades. Since there is currently no reliable method to halt the progression of OA, and the consequence for OA patients is lifetime of painful joints, restricted mobility, reduced quality of life, and ultimately the need for a joint replacement.
The TEB lab focuses on the development of therapies to prevent degeneration of the joint and development of early OA. To date we have focused on the collagenase induced OA (CIOA) model in skeletally mature rats. Intra-articular injection of collagenase creates a short-term acute inflamed environment and weakens the ligaments of the joint. Thus both mechanical and inflammatory aspects of human OA are reflected in the CIOA model. TEB and collaborators have developed a suite of evaluation methods based on uCT, histologic scoring, and functional tests, which together provide a robust and unbiased method assessment of the state of the joint and the efficacy of therapeutics. The CIOA model displays most of the hallmarks of human OA, including increase in cartilage roughness, loss of glycosaminoglycans, osteophyte formation, synovitis and synovial fibrosis, and changes in subchondral bone architecture. The absence of gait abnormalities (Catwalk analysis) and hyperalgesia (Pressure Application Measurement test) underlines the mild phenotype created in the CIOA model. We have used this suite to test the effect of anti-inflammatory drugs and biolubricants on OA progression.
This work is performed in close collaboration with external page Dr. Mikko Finnilä (University of Oulu) and external page Dr. Goncalo Barreto (University of Helsinki). The Oulu method uses contrast enhanced µCT to analyze spatial changes of the joint during disease. The 3D nature of this method allows an assessment of the disease state of the whole joint, which has numerous advantages over histological grading of individual thin tissue sections, which is the current gold standard.
external page

in-vivo OA-Model
Collagenase causes dose-related cartilage degeneration: A) Representative μCT local surface roughness maps of tibial plateaus of two collagenase concentration and the saline control group. Scale bar: 1 mm B) Safranin O staining of medial tibial plateaus that were used in the OARSI CDS grading. Scale bar: 250 μm, 50 μm (insert).  
  • Assessment of whole cartilage surface damage in an osteoarthritis rat model: The Cartilage Roughness Score (CRS) utilizing microcomputed tomography, S Kauppinen, D Fercher, G Barreto, VP Karjaleinen, V Virtanen, L Baixauli-Marin, M Fonti, S Zhang, T Frondelius, P Weber, S Saarakkala, M Zenobi-Wong, MAJ Finnilä, Osteoarthritis Cartilage, 2024, external page https://doi.org/10.1016/j.joca.2024.09.008
  • The Collagenase-Induced Osteoarthritis (CIOA) Model: Where Mechanical Damage Meets Inflammation, Osteoarthritis and Cartilage Open, Patrick Weber, Kajetana Bevc, David Fercher, Sami Kauppinen, Shipin Zhang, Maryam Asadikorayem, Lucia Baixauli Marin, Tianqi Zhang, Tuomas Frondelius, Gian Salzmann, Valentino Bruhin, Jakob Hax, Gonçalo Barreto, Mikko A.J. Finnilä, Marcy Zenobi-Wong, Osteoarthritis and Cartilage Open, 2024, external page https://doi.org/10.1016/j.ocarto.2024.100539  

Contact

David Fercher
  • HPL J 12
  • +41 44 632 31 25

Gewebetechnol. und Biofabrikation
Otto-Stern-Weg 7
8093 Zürich
Switzerland

Dr. Shipin Zhang
  • HPL D 16.2
  • +41 44 633 25 19

Gewebetechnol. und Biofabrikation
Otto-Stern-Weg 7
8093 Zürich
Switzerland

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