Abstract
Elevated levels of growth factors and phospholipids (PLs) have been found in osteoarthritic synovial fluid (SF), although the metabolic regulation of PLs is currently unknown. This study aimed to determine the effects of growth factors on the biosynthesis of PLs by fibroblast-like synoviocytes (FLS) obtained from human osteoarthritic knee joints. Electrospray ionization tandem mass spectrometry was applied to analyse the newly synthesized PLs. In the presence of stable isotope-labelled PL precursors, cultured FLS were treated with either transforming growth factor-β1 (TGF-β1), bone morphogenetic protein (BMP)-2, BMP-4, BMP-7 or insulin-like growth factor-1 (IGF-1) alone or in combination with specific inhibitors of cell signalling pathways. TGF-β1 and IGF-1 markedly stimulated the biosynthesis of phosphatidylcholine (PC) before sphingomyelin (SM) and lysophosphatidylcholine (LPC) species were stimulated. BMPs elaborated less pronounced effects. The BMPs tested have different potentials to induce the biosynthesis of phosphatidylethanolamine (PE) and PE-based plasmalogens. Our study shows for the first time that TGF-β1 and IGF-1 substantially regulate the biosynthesis of PC, SM and LPC in human FLS. The functional consequences of elevated levels of PLs require additional study. The BMPs tested may be joint protective in that they upregulate PE-based plasmalogens that function as endogenous antioxidants against reactive oxygen species.
Highlights
Osteoarthritis (OA) is a widespread degenerative joint disease which affects the entire articular joint including its cartilage, the subchondral bone and the synovium[1,2]
The aim of our study was to investigate for the first time the individual roles which transforming growth factor-β1 (TGF-β1), insulin-like growth factor-1 (IGF-1) and several bone morphogenetic protein (BMP) have on PL classes and species synthesized by fibroblast-like synoviocytes (FLS) obtained from human OA knee joints
Growth factors have been reported to regulate the synthesis of the joint lubricants hyaluronan and lubricin in FLS30–32,34,35, but the impact of these factors on the production of PLs that are involved in joint lubrication is unknown
Summary
Osteoarthritis (OA) is a widespread degenerative joint disease which affects the entire articular joint including its cartilage, the subchondral bone and the synovium[1,2]. Other superfamily members can bind to two or more different types of receptors[9,10]. TGF-β isoforms are expressed in cartilage, bone and synovium, and tissue specific effects have been observed. This growth factor participates in the regulation of chondrocyte maturation and hypertrophy during www.nature.com/scientificreports/. BMP-7 stimulates the synthesis of aggrecan and collagen type II by chondrocytes but blocks the expression of matrix metalloproteinase-13, an enzyme which participates in cartilage destruction[19,20]. Elevated levels of BMP-2 were found in human OA as compared to normal cartilage[21]. The BMP-2 and BMP-7 levels in human plasma and synovial fluid were reported to correlate with OA severity
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