Ingale, Dhanashri, Kulkarni, Priya, Electricwala, Ali, Moghe, Alpana, Kamyab, Sara, Jagtap, Suresh, Martson, Aare, Koks, Sulev ORCID: 0000-0001-6087-6643 and Harsulkar, Abhay
(2021)
Synovium-Synovial Fluid Axis in Osteoarthritis Pathology: A Key Regulator of the Cartilage Degradation Process.
GENES, 12 (7).
989-.
Abstract
Failure of conventional anti-inflammatory therapies in osteoarthritis (OA) underlines the insufficient knowledge about inflammatory mechanisms, patterns and their relationship with cartilage degradation. Considering non-linear nature of cartilage loss in OA, a better understanding of inflammatory milieu and MMP status at different stages of OA is required to design early-stage therapies or personalized disease management. For this, an investigation based on a synovium-synovial fluid (SF) axis was planned to study OA associated changes in synovium and SF along the progressive grades of OA. Gene expressions in synovial-biopsies from different grades OA patients (N = 26) revealed a peak of IL-1β, IL-15, PGE2 and NGF in early OA (Kellgren-Lawrence (KL) grade-I and II); the highest MMP levels were found in advanced stages (KL grade-III and IV). MMPs (MMP-1, 13, 2 and 9) abundance and FALGPA activity estimated in forty SFs of progressive grades showed the maximum protein levels and activity in KL grade-II and III. In an SF challenge test, SW982 and THP1 cells were treated with progressive grade SFs to study the dynamics of MMPs modulation in inflammatory microenvironment; the test yielded a result pattern, which matched with FALGPA and the protein-levels estimation. Inflammatory mediators in SFs served as steering factor for MMP up-regulation. A correlation-matrix of IL-1β and MMPs revealed expressional negative correlation.
Item Type: | Article |
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Uncontrolled Keywords: | FALGPA, inflammatory mediators, Kellgren-Lawrence radiographic grades, MMPs, osteoarthritis, synovial-fluid, synovitis |
Divisions: | Faculty of Health and Life Sciences Faculty of Health and Life Sciences > Institute of Systems, Molecular and Integrative Biology |
Depositing User: | Symplectic Admin |
Date Deposited: | 28 Jan 2022 09:36 |
Last Modified: | 18 Jan 2023 21:14 |
DOI: | 10.3390/genes12070989 |
Open Access URL: | https://doi.org/10.3390/genes12070989 |
Related URLs: | |
URI: | https://livrepository.liverpool.ac.uk/id/eprint/3147752 |