Apolipoprotein-A1 as a damage-associated molecular patterns protein in osteoarthritis: ex vivo and in vitro pro-inflammatory properties.

Dominique De Seny,Denis Malaise,Caroline Le Goff,Sophie Neuville,Edith Charlier,Laurence Lutteri,Jean-Paul Chapelle,Olivier Malaise,Biserka Relic,Michel G Malaise,Gaël Cobraiville

doi:10.1371/journal.pone.0122904

Dominique De Seny, Denis Malaise + Show 9 more

Open Access

https://doi.org/10.1371/journal.pone.0122904

Copy DOI

Abstract

Osteoarthritis (OA) is associated with a local inflammatory process. Dyslipidemia is known to be an underlying cause for the development of OA. Therefore, lipid and inflammatory levels were quantified ex vivo in blood and synovial fluid of OA patients (n=29) and compared to those of rheumatoid arthritis (RA) patients (n=27) or healthy volunteers (HV) (n=35). The role of apolipoprotein A-I (ApoA1) was investigated in vitro on inflammatory parameters using human joint cells isolated from cartilage and synovial membrane obtained from OA patients after joint replacement. Cells were stimulated with ApoA1 in the presence or not of serum amyloid A (SAA) protein and/or lipoproteins (LDL and HDL) at physiological concentration observed in OA synovial fluid. In our ex vivo study, ApoA1, LDL-C and total cholesterol levels were strongly correlated to each other inside the OA joint cavity whereas same levels were not or weakly correlated to their corresponding serum levels. In OA synovial fluid, ApoA1 was not as strongly correlated to HDL as observed in OA serum or in RA synovial fluid, suggesting a dissociative level between ApoA1 and HDL in OA synovial fluid. In vitro, ApoA1 induced IL-6, MMP-1 and MMP-3 expression by primary chondrocytes and fibroblast-like synoviocytes through TLR4 receptor. HDL and LDL attenuated joint inflammatory response induced by ApoA1 and SAA in a ratio dependent manner. In conclusion, a dysregulated lipidic profile in the synovial fluid of OA patients was observed and was correlated with inflammatory parameters in the OA joint cavity. Pro-inflammatory properties of ApoA1 were confirmed in vitro.

Highlights

Osteoarthritis (OA) is one of the most common chronic joint diseases causing substantial health deficits and becoming increasingly more prevalent as the population ages
Busso et al have provided evidences that lipoprotein diffusion from the circulation into the synovial fluid was dependent on the disease type and particles size, and that the permeability of the barrier was increased under inflammatory conditions [22]
Inflammation is largely superior in rheumatoid arthritis (RA) compared to OA, we can hypothesize that local inflammatory process and lipids diffusion inside OA joint cavity can occur, as suggested by their detection in the synovial fluid of OA patients

Summary

Introduction

Osteoarthritis (OA) is one of the most common chronic joint diseases causing substantial health deficits and becoming increasingly more prevalent as the population ages. Articular cartilage is a specific connective tissue covering joint surfaces The synovial membrane is a layer of connective tissue that covers joint cavities and makes lubrication of articular cartilage. Several evidences point to the direction of an altered lipid metabolism as an underlying contributing factor for the development of OA. It is a systemic disorder in which homeostatic dysregulation within the joint structure might be due to adipokines activities [3]. Several similarities between OA and atherosclerosis in their underlying aetiopathogenic factors have suggested chondrocytes as potential foam cells in OA [10]

Methods

Results

Conclusion