ABNORMAL KYNURENINE LEVEL CONTRIBUTES TO THE PATHOLOGICAL BONE FEATURES OF ANKYLOSING SPONDYLITIS

C. Jeon, S. H. Lee, S. Weon, S. H. Choi, T. H. Kim, I. H. Sung, S. JoHanyang University, Hanyang University Institute for Rheumatology Research, Seoul, Korea, Rep. of (South Korea) Hanyang University Hospital, Orthopedic Surgery, Seoul, Korea, Rep. of (South Korea) Hanyang University Hospital for Rheumatic Diseases, Rheumatology, Seoul, Korea, Rep. of (South Korea)  Background Ankylosing spondylitis (AS) exhibits paradoxical bone features typically characterized by new bone formation and systemic bone loss. Objectives Although abnormal kynurenine (Kyn), a tryptophan metabolite, has been closely linked to the disease activity of AS, the distinct role of its pathological bone features remains unknown. Methods Kynurenine sera level was collected from healthy control (n = 22) and AS (n = 87) patients and measured by ELISA. In the AS group, we analyzed and compared the Kyn level based on mSASSS scores, MMP13, and OCN. Under osteoblast differentiation, the effect of Kyn in AS-osteoprogenitors resulted in cell proliferation, alkaline phosphatase activity, bone mineralization-related alizarin red s (ARS), von kossa (VON), hydroxyapatite (HA) staining, and mRNA expression markers (ALP, RUNX2, OCN, and OPG) for bone formation. TRAP staining was used for osteoclast formation in RANKL-mediated RAW264.7 cells. Results Kyn sera level was significantly elevated in the AS group compared to the healthy control group. In addition, Kyn sera level was correlated with mSASSS score (r = 0.03888, p = 0.067), MMP13 (r = 0.0327, p = 0.093), and OCN (r = 0.0436, p = 0.052). During osteoblast differentiation, treatment with Kyn exhibited no difference in cell proliferation and alkaline phosphate (ALP) activity for bone matrix maturation but promoted ARS, VON, and HA staining for bone mineralization. Interestingly, osteoprotegerin (OPG) and OCN expression was augmented in the presence of Kyn treatment during differentiation. In growth medium, Kyn treatment of osteoprogenitors resulted in induction of OPG mRNA, protein expression, and AhR response genes (AhRR, CYP1b1, and TIPARP). Secreted OPG proteins were observed in the supernatant of osteoprogenitors treated with Kyn. Notably, the supernatant addition to osteoclastogenesis interrupted the TRAP-positive osteoclast formation of RANKL-mediated RAW264.7 cells and reduced osteoclast differentiation markers. Conclusion Our results revealed that elevated Kyn level increased the bone mineralization of osteoblast differentiation in AS and decreased RANKL-mediated osteoclast differentiation by inducing OPG expression, suggesting a potential therapeutic target where abnormal Kyn level could be involved in pathological bone features of AS. REFERENCES: NIL. Acknowledgements: NIL. Disclosure of Interests None Declared. Keywords: Spondyloarthritis DOI: 10.1136/annrheumdis-2023-eular.3439Citation: , volume 82, supplement 1, year 2023, page 1229Session: Spondyloarthritis - aetiology, pathogenesis and animal models (Publication only)