Synovium-Synovial Fluid Axis in Osteoarthritis Pathology: A Key Regulator of the Cartilage Degradation Process
| Autor: | Sulev Kõks, Aare Märtson, Suresh Jagtap, Dhanashri R Ingale, Alpana Moghe, Ali Electricwala, Sara Kamyab, Abhay Harsulkar, Priya Kulkarni |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Male
0301 basic medicine Pathology medicine.medical_specialty inflammatory mediators Interleukin-1beta Regulator Osteoarthritis Matrix metalloproteinase QH426-470 Cartilage degradation Dinoprostone Article Kellgren–Lawrence radiographic grades 03 medical and health sciences 0302 clinical medicine synovial-fluid Synovitis Nerve Growth Factor Synovial Fluid Genetics Humans Medicine Synovial fluid Genetics (clinical) Interleukin-15 030203 arthritis & rheumatology business.industry Cartilage Synovial Membrane Osteoarthritis Knee medicine.disease osteoarthritis 030104 developmental biology medicine.anatomical_structure FALGPA Female MMPs Matrix Metalloproteinase 1 Negative correlation business synovitis Oligopeptides |
| Zdroj: | Genes Volume 12 Issue 7 Genes, Vol 12, Iss 989, p 989 (2021) |
| ISSN: | 2073-4425 |
| DOI: | 10.3390/genes12070989 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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