Catabolic mediators from TLR2-mediated proteoglycan aggrecan peptide-stimulated chondrocytes are reduced by Lactobacillus-conditioned media

• Published in: Scientific reports Vol. 14; no. 1; pp. 18043 - 15
• Main Authors: Sengprasert, Panjana, Waitayangkoon, Palapun, Kamenkit, Ousakorn, Sawatpanich, Ajcharaporn, Chaichana, Thiamjit, Wongphoom, Jutamas, Ngarmukos, Srihatach, Taweevisit, Mana, Lotinun, Sutada, Tumwasorn, Somying, Tanavalee, Aree, Reantragoon, Rangsima
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 05-08-2024; Nature Publishing Group; Nature Portfolio
• Subjects: 631/250/262/2106; 631/80/304; 631/80/86; 692/4023/1670/407; 692/698/1671/1354; ADAMTS4 Protein - metabolism; Aggrecan; Aggrecans - metabolism; Anti-inflammatory agents; Cartilage; Cartilage diseases; Cells, Cultured; Chondrocytes; Chondrocytes - drug effects; Chondrocytes - metabolism; Culture Media, Conditioned - pharmacology; Enzymes; Extracellular matrix; Extracellular signal-regulated kinase; Humanities and Social Sciences; Humans; Hypertrophy; Interstitial collagenase; Intracellular signalling; Lactobacillus; Lactobacillus - metabolism; MAP kinase; Matrix metalloproteinase; Matrix Metalloproteinase 1 - genetics; Matrix Metalloproteinase 1 - metabolism; multidisciplinary; NF-KappaB Inhibitor alpha - metabolism; NF-κB protein; Osteoarthritis; Osteoarthritis - metabolism; Osteoarthritis - pathology; Peptides; Peptides - metabolism; Peptides - pharmacology; Phosphorylation; Proteoglycans; Proteoglycans - metabolism; Proteoglycans - pharmacology; Proteolysis; Science; Science (multidisciplinary); Signal Transduction - drug effects; Stat3 protein; STAT3 Transcription Factor - metabolism; TLR2 protein; Toll-Like Receptor 2 - metabolism; Toll-like receptors; Transcription activation; Transcriptomics; γ-Interferon
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-024-68404-9

In osteoarthritis (OA), extracellular matrix (ECM) digestion by cartilage-degrading enzymes drives cartilage destruction and generates ECM fragments, such as proteoglycan aggrecan (PG) peptides. PG peptides have been shown to induce immunological functions of chondrocytes. However, the role of PG peptides in stimulating catabolic mediators from chondrocytes has not been investigated. Therefore, we aim to determine the effects and its mechanism by which PG peptides induce chondrocytes to produce catabolic mediators in OA. Human chondrocytes were stimulated with IFNγ and various PG peptides either (i) with or (ii) without TLR2 blockade or (iii) with
Lactobacillus
species-conditioned medium (LCM), a genus of bacteria with anti-inflammatory properties. Transcriptomic analysis, cartilage-degrading enzyme production and TLR2-intracellular signaling activation were investigated. Chondrocytes treated with PG peptides p16-31 and p263-280 increased expression levels of genes associated with chondrocyte hypertrophy, cartilage degradation and proteolytic enzyme production. TLR2 downstream signaling proteins (STAT3, IkBα and MAPK9) were significantly phosphorylated in p263-280 peptide-stimulated chondrocytes. MMP-1 and ADAMTS-4 were significantly reduced in p263-280 peptides-treated condition with TLR2 blockade or LCM treatment. Phosphorylation levels of IkBa, ERK1/2 and MAPK9 were significantly decreased with TLR2 blockade, but only phosphorylation levels of MAPK9 was significantly decreased with LCM treatment. Our study showed that PG peptide stimulation via TLR2 induced cartilage-degrading enzyme production via activation of MAPK, NFκB and STAT3 pathways.