Exposure to fermentation supernatant of Staphylococcus aureus accelerated dedifferentiation of chondrocytes and production of antimicrobial peptides

• Published in: Journal of orthopaedic research Vol. 36; no. 1; pp. 443 - 451
• Main Authors: Li, Shuaijun, Zhang, Yun, Sun, Yidan, Cao, Weigang, Cui, Lei
• Format: Journal Article
• Language: English
• Published: United States 01.01.2018
• Subjects: Animals; Anti-Infective Agents - metabolism; antimicrobial peptides; beta-Defensins - biosynthesis; Cathelicidins - biosynthesis; Cell Dedifferentiation; Cells, Cultured; chondrocytes; Chondrocytes - cytology; Chondrocytes - immunology; Chondrocytes - metabolism; Cytokines - genetics; dedifferentiation; Fermentation; Mice; Mice, Inbred C57BL; septic arthritis; Staphylococcus aureus; Staphylococcus aureus - metabolism; dedifferentiation; chondrocytes; septic arthritis; Staphylococcus aureus; antimicrobial peptides
• ISSN: 0736-0266; 1554-527X
• DOI: 10.1002/jor.23605

ABSTRACT Staphylococcus aureus (S. aureus) is the most popular pathogen found in septic arthritis. Despite bacteria was eradicated from joint cavity during acute infection, destruction of articular cartilage often continues for years, leading to permanent joint damage. The mechanism responsible for this consistent catabolic reaction in septic arthritis remains unclear. Here, we found that fermentation supernatant (FS) of S. aureus accelerated dedifferentiation of chondrocytes and induced expression of catabolic factors including A Disintegrin‐like and Metalloproteinase with Thrombospondin‐1 motifs 5, NO synthase 2, matrix metalloproteinase‐3, ‐13. In response to FS of S. aureus stimulation, expression of antimicrobial peptides (AMPs) including β‐defensin‐1, ‐2, ‐3, ‐4, cathelicidin antimicrobial peptide (CAMP) in dedifferentiated chondrocytes was significantly higher than that in chondrocytes which maintained their differentiated phenotype. Among AMPs detected, expression of CAMP in dedifferentiated chondrocytes was observed to increase 170 times higher than that in differentiated ones. When exposed to FS of S. aureus, expression of interleukin (IL)‐1β, IL‐17F, and IL‐22 were remarkably increased in dedifferentiated chondrocytes. These results indicated that dedifferentiation of chondrocytes caused by exposure to S. aureus might be responsible for secondary osteoarthritis (OA) after acute S. aureus infection in joint. While, one potential benefit of dedifferentiation resulted from S. aureus exposure is that chondrocytes initiates a self‐protective responsiveness by producing more AMPs against bacterial infection. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:443–451, 2018. Li et al. show that fermentation supernatant of S. aureus induced expression of IL‐1βand accelerated dedifferentiation of chondrocytes with suppression of Sox9, COLII, ACAN, and increase of COLI, COLIII, MMP3, MMP13, NOS2, ADAMTS5. More importantly, we found that expression of AMPs including β‐defensin‐1, ‐2, ‐3, ‐4, CAMP in dedifferentiated chondrocytes was significantly higher than differentiated chondrocytes.