The Effect of Dexamethasone, Adrenergic and Cholinergic Receptor Agonists on Phospholipid Metabolism in Human Osteoarthritic Synoviocytes.

Katarzyna Sluzalska,Bernd Ishaque,Gerhard Liebisch,Juergen Steinmeyer,Markus Rickert,Gerd Schmitz

doi:10.3390/ijms20020342

Abstract

Phospholipids (PLs) possess the unique ability to contribute to synovial joint lubrication. The aim of our study was to determine for the first time the effect of dexamethasone and some adrenergic and cholinergic agonists on the biosynthesis and release of PLs from human fibroblast-like synoviocytes (FLS). Osteoarthritic human knee FLS were treated with dexamethasone, terbutaline, epinephrine, carbachol, and pilocarpine, or the glucocorticoid receptor antagonist RU 486. Simultaneously PL biosynthesis was determined through the incorporation of stable isotope-labeled precursors into PLs. Radioactive isotope-labeled precursors were used to radiolabel PLs for the subsequent quantification of their release into nutrient media. Lipids were extracted and quantified using electrospray ionization tandem mass spectrometry or liquid scintillation counting. Dexamethasone significantly decreased the biosynthesis of phosphatidylcholine, phosphatidylethanolamine (PE), PE-based plasmalogen, and sphingomyelin. The addition of RU 486 abolished these effects. A release of PLs from FLS into nutrient media was not recognized by any of the tested agents. None of the adrenergic or cholinergic receptor agonists modulated the PL biosynthesis. We demonstrate for the first time an inhibitory effect of dexamethasone on the PL biosynthesis of FLS from human knees. Moreover, our study indicates that the PL metabolism of synovial joints and lungs are differently regulated.

Highlights

Phospholipids (PLs) are important molecules that participate in many biological processes
Our present study attempted to determine the effect of the corticosteroid dexamethasone on the PL metabolism of human fibroblast-like synoviocytes (FLS) derived from OA knee joints
Our results demonstrate that dexamethasone inhibited the biosynthesis of PLs, but did not influence their release from FLS

Summary

Introduction

Phospholipids (PLs) are important molecules that participate in many biological processes. Due to their structure, they have the ability to reduce surface tension to very low levels [1,2]. They have the ability to reduce surface tension to very low levels [1,2] This feature makes them perfect candidates as lung surfactants as well as synovial joint lubricants. Several studies reported that fibroblast-like synoviocytes (FLS) are able to synthesize and release synovial joint lubricating molecules such as PLs, hyaluronan, and lubricin [2,8,9,10,11]. Our group was able to demonstrate an association between alterations in synovial lubricant composition and the disease state of the joint [11]

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