Modeling Cartilage Degeneration by Combining Systems Biology and Biomechanical Approaches

• Applicant: Dr. Michael Neidlin
• Subject Area: Orthopaedics, Traumatology, Reconstructive Surgery ; Bioinformatics and Theoretical Biology ; Medical Physics, Biomedical Technology
• Term: from 2017 to 2019
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 387071423

• Final Report Year: 2019

Final Report Abstract

Osteoarthritis (OA) is a multifactorial whole joint disease affecting a big amount of the population with no medication strategies beyond pain-relief treatments. The goal of the project was to use a combination of systems biology and biomechanics in order to better understand cartilage degradation and leverage drug discovery in OA. In the scope of the project an innovative computational and experimental pipeline was developed that can be applied to drug discovery studies to treat osteoarthritis related cartilage degradation. On the computational front a numerical framework was developed that uses genomic information of healthy and OA patients in order to suggest drugs that affect genes and molecular functions of pathological tissues. Here systems biology using network-based approaches and graph theoretical considerations was employed. On the experimental front, an innovative in vitro model has been developed that measures protein release patterns of healthy and OA cartilage and uses this multidimensional data to classify the state of the tissue. This methodology allows an easy way to screen pharmaceutical compounds and investigate the still unexplored field of combination therapy for OA. At last, experimental and computational biomechanics was used to quantify the mechanical changes of OA cartilage that has been objected to treatment with pharmaceutical compounds. In summary, the presented work shows up the possibilities that arise from systematic investigations of biological systems and paves the way to include macroscopic biomechanical analyses in molecular biological studies of soft tissues.

Publications

• A device for high-throughput monitoring of degradation in soft tissue samples. J Biomech. 2018;74:180–6
  Tzeranis DS, Panagiotopoulos IA, Gkouma S, Kanakaris G, Georgiou NA, Vaindirlis N, Neidlin M, et al.
  
• Investigations of cytokine interplay with an in vitro model of osteoarthritis. Osteoarthritis and Cartilage 26, S111, 2018
  Neidlin M, Chantzi E, Macheras G, Gustafsson MG, Alexopoulos LG
  
• An ex vivo tissue model of cartilage degradation suggests that cartilage state can be determined from secreted key protein patterns. PLoS ONE 14(10): e0224231. 2019
  Neidlin M, Chantzi E, Macheras G, Gustafsson MG, Alexopoulos LG
  
• Multi-tissue network analysis for drug prioritization in knee osteoarthritis. Scientific Reports, 9:15176, 2019
  Neidlin M, Dimitrakopoulou S, Alexopoulos LG