ACR Meeting Abstracts

ACR Meeting Abstracts

Abstract Number: 2807

Transcriptome Profiling of Synovium from Patients with Psoriatic Arthritis or Osteoarthritis Using RNA Sequencing Provides Insights into Disease Mechanisms Involved in Heterotopic Ossification with Potential Therapeutic Implications

Jennifer Belasco1, Steven R. Goldring2, Kelly McHugh3, James G. Krueger4, Areille Fein2, Sandra Garcet5, Mayte Suarez-Farinas4, Lisa Mandl6 and Yupu Liang5, 1Krueger Laboratory, Rockefeller University, New York, NY, 2Hospital for Special Surgery, New York, NY, 3Rheumatology, Hospital for Special Surgery, New York, NY, 4Krueger Laboratory, The Rockefeller University, New York, NY, 5The Rockefeller University, New York, NY, 6Department of Rheumatology, Hospital for Special Surgery, New York, NY

Meeting: 2015 ACR/ARHP Annual Meeting

Date of first publication: September 29, 2015

Keywords:

Session Information

Date: Tuesday, November 10, 2015

Title: Spondylarthropathies and Psoriatic Arthritis Pathogenesis, Etiology Poster I

Session Type: ACR Poster Session C

Session Time: 9:00AM-11:00AM

Background/Purpose: Up to 44% of patients undergoing total hip arthroplasty (THA) show radiographic evidence of heterotopic ossification (HO). Patients with psoriatic arthritis (PsA) and a subset of patients with osteoarthritis (OA) demonstrate an increased risk of HO after THA.  The molecular and cellular mechanisms responsible for HO are poorly defined.  We conducted a comprehensive genomic and molecular comparison of synovium taken from patients at the time of THA. We compared three groups of patients: osteoarthritis (OA) patients who had developed HO after a previous THA, OA patients who had not developed HO after a previous THA, and PsA patients undergoing a first THA.

Methods: Synovium samples were obtained at the time of THA from three groups: OA patients with previous HO after a primary THA (n= 7), or OA patients without HO (n=7) after a primary THA; and patients with PsA undergoing an initial THA (n=7). RNA-seq was performed to identify shared and differentially expressed genes (DEGs).  DEGs were considered with a cut-off of fold change >2.0 and false discovery rate <0.05.  Ingenuity Pathway Analysis (IPA) was utilized to identify canonical pathways among shared and DEGs. 

Results: A comparison of PsA vs. OA and HO vs. OA transcripts revealed 631 differentially expressed genes unique to the PsA vs. OA group and 91 differentially expressed genes unique to the HO vs. OA group.  76 genes were shared between these groups.  When PsA is directly compared to HO there are 386 shared genes.  The top canonical pathways from IPA based on these shared genes include IL12 signaling and production in macrophages, 4-IBB signaling in T lymphocytes, Inhibition of angiogenesis by TSP1, Nitric oxide signaling in the cardiovascular system, Leptin signaling in obesity, BMP signaling pathway, and TGFβ signaling.

Conclusion: In this study we show similarities and differences in gene expression of synovium from patients with OA with HO, OA without HO, and PsA. To our knowledge, this is the first study to use RNA-seq to define the transcriptomes of synovium in these conditions.  It is also the first study to compare these populations.  Genes shared between HO and PsA might suggest a common bone anabolic pathway and direct future therapies for these conditions.

Disclosure: J. Belasco, None; S. R. Goldring, Fidia Farmaceutici, Janssen Pharmaceutical,BoneTherapeutics,Novartis, 5; K. McHugh, None; J. G. Krueger, None; A. Fein, None; S. Garcet, None; M. Suarez-Farinas, None; L. Mandl, Boehringer Ingelheim, 2; Y. Liang, None.

To cite this abstract in AMA style:

Belasco J, Goldring SR, McHugh K, Krueger JG, Fein A, Garcet S, Suarez-Farinas M, Mandl L, Liang Y. Transcriptome Profiling of Synovium from Patients with Psoriatic Arthritis or Osteoarthritis Using RNA Sequencing Provides Insights into Disease Mechanisms Involved in Heterotopic Ossification with Potential Therapeutic Implications [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). https://acrabstracts.org/abstract/transcriptome-profiling-of-synovium-from-patients-with-psoriatic-arthritis-or-osteoarthritis-using-rna-sequencing-provides-insights-into-disease-mechanisms-involved-in-heterotopic-ossification-with-po/. Accessed .

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