Toll‐like receptor involvement in adolescent scoliotic facet joint degeneration

• Published in: Journal of cellular and molecular medicine 2020-10, Vol.24 (19), p.11355-11365
• Main Authors: Bisson, Daniel G., Sheng, Kai, Kocabas, Semsi, Krock, Emerson, Teles, Alisson, Saran, Neil, Ouellet, Jean A., Haglund, Lisbet
• Format: Article
• Language: English
• Subjects: Adolescent; adolescent idiopathic scoliosis; Adult; Agonists; Alarmins - metabolism; Benzaldehydes - pharmacology; Biopsy; Cartilage; Cartilage diseases; Chondrocytes; Chondrocytes - drug effects; Chondrocytes - metabolism; Chondrocytes - pathology; Cytokines; Degeneration; Extracellular matrix; Extracellular Matrix - drug effects; Extracellular Matrix - metabolism; facet joint; Female; Gene expression; Gene Expression Regulation - drug effects; Heterocyclic Compounds, 4 or More Rings - pharmacology; Histology; Humans; Inflammation; Inflammation - genetics; Inflammation - pathology; Male; metalloproteases; Middle Aged; Original; Osteoarthritis; Peptides; Proteins; Proteoglycans; S100 Proteins - metabolism; Scoliosis; Scoliosis - genetics; Scoliosis - metabolism; Scoliosis - pathology; Stroke; TLR2 protein; Toll-like receptors; Toll-Like Receptors - genetics; Toll-Like Receptors - metabolism; Vanillin; Young Adult; Zygapophyseal Joint - drug effects; Zygapophyseal Joint - metabolism; Zygapophyseal Joint - pathology
• ISSN: 1582-1838; 1582-4934
• DOI: 10.1111/jcmm.15733

Facet joint osteoarthritis is prevalent in young patients with adolescent idiopathic scoliosis (AIS) and might contribute to back pain. Toll‐like receptors (TLR) have been linked to cartilaginous tissue degeneration but their involvement in facet joint osteoarthritis in AIS patients is still unknown. We compared baseline gene expression levels of TLRs ‐1, ‐2, ‐4, and ‐6 in scoliotic and non‐scoliotic chondrocytes and found higher expression levels in scoliotic chondrocytes with significantly higher TLR2 levels. Furthermore, TLR expression correlated strongly and significantly with inflammatory and catabolic markers in scoliotic but not in non‐scoliotic chondrocytes. TLR activation with a synthetic TLR2/6 agonist resulted in a robust induction and release of pro‐inflammatory and catabolic factors which exacerbated proteoglycan loss in scoliotic but not in non‐scoliotic cartilage. We also detected a higher abundance of alarmins including S100A8/9 and biglycan in scoliotic cartilage. Finally, the small‐molecule antagonists Sparstolonin B and o‐Vanillin reduced catabolism following induction with naturally occurring alarmins and the synthetic TLR2/6 agonist. The high baseline expression, robust responsiveness and strong and significant correlation with proteases and pro‐inflammatory cytokines suggest that TLRs are key regulators of facet joint degeneration in AIS. Blocking their activity could therefore potentially modify disease progression.