Biosynthesis and release of phospholipids by fibroblast-like synoviocytes from human osteoarthritic knee joint

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In human joints, phospholipids (PLs) are produced and released by fibroblast-like synoviocytes (FLS), but the regulatory mechanisms are not well understood. Elevated cytokines, growth factors, and PLs are found in synovial fluid (SF) during osteoarthritis (OA). This study hypothesized that PL metabolism in FLS is influenced by agents present in OA SF. Two in vitro models were developed to examine PL biosynthesis and release, assessing the effects of various agents. FLS were cultured in DMEM with stable isotope-labelled precursors to measure PL biosynthesis, while the release was studied using radiolabelled precursors. Lipids were extracted and quantified using mass spectrometry and liquid scintillation counting. Results revealed that IL-1β stimulated the biosynthesis of phosphatidylethanolamine (PE) and PE-based plasmalogens, while TNFα only induced PE biosynthesis. Bone morphogenetic proteins (BMPs) also promoted several PE and PE P species. In vivo, PE P may protect against cartilage destruction, while elevated PE could induce apoptosis in hypertrophic FLS. Growth factors like TGF-β1, IGF-1, and BMP-2 enhanced phosphatidylcholine (PC) biosynthesis, potentially aiding joint lubrication. Dexamethasone decreased PE biosynthesis. Although PL release was time-dependent, tested agents did not affect it, indicating a need for further investigation. Overall, cytokines and growth factors regulate PL biosynthesis, contributing to alte