IL-23p19 in osteoarthritic pain and disease

• Published in: Osteoarthritis and cartilage Vol. 32; no. 11; pp. 1413 - 1418
• Main Authors: Lee, Kevin M.-C., Lupancu, Tanya, Achuthan, Adrian A., de Steiger, Richard, Hamilton, John A.
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 04.06.2024
• Subjects: Experimental arthritis; IL-23; Knee osteoarthritis; Pain; Knee osteoarthritis; Pain; IL-23; Experimental arthritis
• ISSN: 1063-4584; 1522-9653; 1522-9653
• DOI: 10.1016/j.joca.2024.05.011

We have previously reported that the interleukin-23 p19 subunit (IL-23p19) is required for experimental inflammatory arthritic pain-like behavior and disease. Even though inflammation is often a characteristic feature of osteoarthritis (OA), IL-23 is not usually considered as a therapeutic target in OA. We began to explore the role of IL-23p19 in OA pain and disease utilizing mouse models of OA and patient samples. The role of IL-23p19 in two mouse models of OA, namely collagenase-induced OA and monosodium iodoacetate-induced OA, was investigated using gene-deficient male mice. Pain-like behavior and arthritis were assessed by relative static weight distribution and histology, respectively. In knee synovial tissues from a small cohort of human OA patients, a correlation analysis was performed between IL-23A gene expression and Oxford knee score (OKS), a validated Patient Reported Outcome Measure. We present evidence that i) IL-23p19 is required for the development of pain-like behavior and optimal disease, including cartilage damage and osteophyte formation, in two experimental OA models and ii) IL-23A gene expression in OA knee synovial tissues correlates with a lower OKS (r = −0.742, p = 0.0057). The findings support the possible targeting of IL-23 as a treatment for OA pain and disease progression.