1789: Microtrauma Exacerbates Arthritis and Enthesitis in Curdlan-administered SKG Mice by Inducing FGF16 Expresssion

Seung Hoon Lee¹, Chanhyeok Jeon¹, Sungsin Jo¹ and Tae-Hwan Kim², ¹Hanyang University Institute for Rheumatology Research, Seoul, South Korea, ²Department of Rheumatology, Hanyang University Hospital for Rheumatic Diseases, Seoul, South Korea

Background/Purpose: Microtrauma might be considered a crucial of various environmental factors in AS, but there is still unknown whether microtrauma has a direct/indirect role in the pathogenesis of AS.

Methods: To induce microtrauma injuries, right hindlimb of male SKG mouse was immobilized by a surgical sticking plaster and pipette tip for a week. After this period, the fixed tip was removed from ankle and the mouse was intraperitoneally injected with 3 mg curdlan. Left and Right ankles were considered microtraumatized and non-microtraumatized group, respectively. We monitored clinical arthritis to score it every week for 5 weeks. At 6 weeks, the physical changes in ankles and sacroiliac joints were evaluated by histological and micro-CT analysis. Primary muscle cells were induced by shear stress for a day to mimic microtrauma and conducted RNA-sequencing.

Results: After curdlan injection in SKG mice, the left ankle was microtraumatized and showed an increase in frequency and severity of arthritis and enthesitis when compared to the non-microtraumatized right ankle. Also, as revealed by micro-CT analysis, the inflamed bone volume was decreased in the heel of non-microtraumatized right ankle, whereas dramatically increased in heel of microtraumatized left ankle. Moreover, TNFa expression in enthesis and arthritis of ankle using IHC were much higher in microtraumatized left ankle than non-microtraumatized right ankle. Intriguingly, the SI joints of the left hip were shown cartilage fusion in the microtraumatized left as compared to the non-microtraumatized right. When RNA-sequencing data of shear stress was compared to non-stress groups, we found that the FGF16 gene is a top rank in the stress group. The expression of FGF16 was significantly elevated in the femur muscle of microtraumatized left ankle.

Conclusion: Here we showed that microtrauma at ankle using immobilization contributes to severity arthritis and enthesitis at ankle and induction of FGF16 in muscle of curdlan-injected SKG mice.


S. Lee: None; C. Jeon: None; S. Jo: None; T. Kim: None.