Summary
This research project aims to precisely define proteolytic events and mechanisms in post-traumatic osteoarthritis (PTOA) using degradomics to enable early detection, risk assessment, and drug development.
Degradomics of proteolytic mechanisms in post-traumatic osteoarthritis
US · IL
NIH
grant
awarded
#nih-1R01AR085047-01A1
What they want
The objective of this proposal is to precisely define proteolytic events on the proteome scale (i.e., the degradome) and proteolytic mechanisms along the timeline of PTOA. This involves three main objectives: 1. To quantitatively define proteolytic impact and mechanisms in PTOA by quantitative analysis of synovial fluid degradomes in humans with anterior cruciate ligament (ACL) injury and an experimental equine model of PTOA. 2. To precisely define specific proteolytic contributions by key proteases to PTOA/OA. 3. To develop proteolysis-oriented Data-Independent Acquisition Mass Spectrometry (DIA-MS) as a high-throughput, scalable technology, to be applied initially for quantitative degradomics of synovial fluid, with the eventual goal of identifying PTOA proteolytic signatures in blood.
Deliverables
- Time- and protease-resolved degradomic signatures of PTOA
- New insights on osteoarthritis mechanisms
- New technology for early diagnosis, risk assessment, and drug development
Technical requirements
- Degradomics
- Proteomics
- Data-independent acquisition mass spectrometry (DIA-MS)
- Spectral libraries of knee OA synovial fluid
