Session Type: Abstract Submissions
Session Time: 5:30PM-7:00PM
Methods: Chromatin immunoprecipitation sequencing was performed to determine the (super-)enhancer repertoire of JIA patient SF-derived monocytes. Gene expression of SF-derived monocytes was analyzed using RNA-sequencing. Osteoclastogenesis of monocytes was assessed by osteoclast differentiation assays followed by tartrate-resistant acid phosphatase (TRAP) staining and bone resorption measurements.
Results: The (super-)enhancer profile of JIA patient-derived monocytes demonstrated that osteoclast-related genes are associated with an increased enhancer or super-enhancer in JIA compared to healthy control (HC) monocytes, suggesting that the osteoclast pathway might play a crucial role in JIA monocytes. This is in agreement with the observation that osteoclast-associated genes are enriched in genes that are upregulated in JIA SF-derived monocytes, indicating that osteoclast differentiation might be increased. Indeed, differentiation of HC monocytes in the presence of SF enhanced the formation of osteoclasts.
Conclusion: Our results indicate that monocytes obtained from the inflammatory site of JIA patients display increased osteoclastogenesis, resulting in more bone degradation. This enhanced osteoclast differentiation is likely to be the consequence of the inflammatory environment present in the joint. Altogether, therapies aimed at inhibiting the differentiation of monocytes into osteoclasts, for example by inhibiting inflammatory mediators present in the SF, might reduce bone loss and thus improve joint function in JIA patients.
To cite this abstract in AMA style:Peeters J, Boltjes A, Vervoort S, Coffer P, Vastert B, van Wijk F, Mokry M, de Vries T, van Loosdregt J. Epigenetic Profiling Of Juvenile Idiopathic Arthritis (JIA) Synovial Fluid Monocytes Points Towards a Role For Monocytes In Bone Damage [abstract]. Arthritis Rheumatol. 2017; 69 (suppl 4). https://acrabstracts.org/abstract/epigenetic-profiling-of-juvenile-idiopathic-arthritis-jia-synovial-fluid-monocytes-points-towards-a-role-for-monocytes-in-bone-damage/. Accessed October 22, 2020.
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/epigenetic-profiling-of-juvenile-idiopathic-arthritis-jia-synovial-fluid-monocytes-points-towards-a-role-for-monocytes-in-bone-damage/