Synovium-Synovial Fluid Axis in Osteoarthritis Pathology: A Key Regulator of the Cartilage Degradation Process

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-.

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Official URL: http://dx.doi.org/10.3390/genes12070989

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
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:	Author Publisher
URI:	https://livrepository.liverpool.ac.uk/id/eprint/3147752