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

Dhanashri Ingale,Sara Kamyab,Sulev Koks,Abhay Harsulkar,Priya Kulkarni,Suresh Jagtap,Alpana Moghe,Aare Martson,Ali Electricwala

doi:10.3390/genes12070989

Dhanashri Ingale, Sara Kamyab + Show 7 more

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https://doi.org/10.3390/genes12070989

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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.

Highlights

Osteoarthritis (OA) is the most prevalent whole-joint disorder that exists in the elderly population
Peak expressions of IL-1β and IL-15 in KL gradeI synovium indicated that the regulators of the inflammation were expressed higher at early stage that provides a biochemical trigger even before appearance of undoubted clinical signatures of OA
The highest PGE2 was found in KL grade-II samples, immediately in the stage of peak IL-1β, the main inducer of PGE2

Summary

Introduction

Osteoarthritis (OA) is the most prevalent whole-joint disorder that exists in the elderly population. OA pathology is not fully understood, it is a multifactorial disorder marked by several cellular and molecular changes, such as an imbalance between cartilage anabolism and catabolism, chondrocytes hypertrophy and death, infiltration of macrophages and activation of immune responses and synovial inflammation and hypertrophy. All together, these pathological changes lead to a gradual loss of articular cartilage. These pathological changes lead to a gradual loss of articular cartilage Clinical symptoms, such as joint stiffness, warmth, pain, and joint effusion indicate a presence of inflammation in OA joints [1]. The gathered evidence suggests that mononuclear infiltration and over expression of inflammatory mediators in synovium are seen in early OA and predate radiographic damage in OA [5]

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