Our understanding of the cellular and molecular pathways driving the pathogenesis in ankylosing spondylitis (AS) is still very incomplete. One of the key challenges in management of AS is lack of specific markers of disease activity. Aberrant expression of microRNAs (miRNAs) has been identified in various diseases. Recent studies demonstrated that miRNAs can be detected in the circulation and serve as potential biomarkers of various diseases. Moreover, the detection of circulating miRNAs can provide important novel information concerning diseases. At present there are no studies that have established a miRNA based signature profile in patients with AS. Given these findings, we hypothesize that patients with AS have aberrantly expressed circulating miRNAs reflective of underlying disease and inflammation and these dysregulated miRNAs can be detected through miRNA expression profiling. We further hypothesize that certain specific dysregulated candidate miRNAs in plasma of patients with AS will correlate with disease activity measures like Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and Ankylosing Spondylitis Disease Activity Score (ASDAS). These hypotheses will be addressed in the experiments of the following specific Aims: (1) to determine the expression profile of miRNAs in plasma of patients with AS and compare it with healthy, age and sex-matched controls. (2) To test whether the expression of the specific miRNAs identified in aim-1 correlates with disease activity in AS as measured by BASDAI and ASDAS. Should the exploratory study reveal a correlation between specific miRNAs in the plasma of patients with AS and disease activity measures, they may represent potential biomarkers of disease activity in AS. These potential biomarkers of disease activity in AS can be validated in future large clinical studies and may have significant impact on management of AS.

Public Health Relevance

These exploratory studies are relevant to public health for two reasons. The proposed study involves patients with Ankylosing spondylitis (AS), a relatively common inflammatory arthritis which primarily involves axial skeleton, resulting in pain, limitation of spinal mobility, spinal fractures and deformities. It has a considerable impact on patient functioning and quality of life. One of the key challenges in management of AS is the lack of specific markers of disease activity. The studies may establish microRNA (miRNAs) based signature profile in plasma of patients with AS and also identify the predicted target pathways of the differentially expressed miRNAs. It may help us to better understand the pathogenesis of this disease. Also, dysregulated miRNAs may represent a novel group of potential biomarkers of disease activity in plasma of patients with AS.

National Institute of Health (NIH)
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Exploratory/Developmental Grants (R21)
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Arthritis, Connective Tissue and Skin Study Section (ACTS)
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Wang, Yan Z
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Case Western Reserve University
Internal Medicine/Medicine
Schools of Medicine
United States
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Khan, Nazir M; Haqqi, Tariq M (2018) Epigenetics in osteoarthritis: Potential of HDAC inhibitors as therapeutics. Pharmacol Res 128:73-79
Haseeb, Abdul; Makki, Mohammad Shahidul; Khan, Nazir M et al. (2017) Deep sequencing and analyses of miRNAs, isomiRs and miRNA induced silencing complex (miRISC)-associated miRNome in primary human chondrocytes. Sci Rep 7:15178
Akhtar, Nahid; Khan, Nazir M; Ashruf, Omer S et al. (2017) Inhibition of cartilage degradation and suppression of PGE2 and MMPs expression by pomegranate fruit extract in a model of posttraumatic osteoarthritis. Nutrition 33:1-13
Haseeb, Abdul; Ansari, Mohammad Yunus; Haqqi, Tariq M (2017) Harpagoside suppresses IL-6 expression in primary human osteoarthritis chondrocytes. J Orthop Res 35:311-320
Haseeb, Abdul; Khan, Nazir M; Ashruf, Omer S et al. (2017) A Polyphenol-rich Pomegranate Fruit Extract Suppresses NF-?B and IL-6 Expression by Blocking the Activation of IKK? and NIK in Primary Human Chondrocytes. Phytother Res 31:778-782
Khan, Nazir M; Haseeb, Abdul; Ansari, Mohammad Y et al. (2017) Wogonin, a plant derived small molecule, exerts potent anti-inflammatory and chondroprotective effects through the activation of ROS/ERK/Nrf2 signaling pathways in human Osteoarthritis chondrocytes. Free Radic Biol Med 106:288-301
Khan, Nazir M; Ansari, Mohammad Y; Haqqi, Tariq M (2017) Sucrose, But Not Glucose, Blocks IL1-?-Induced Inflammatory Response in Human Chondrocytes by Inducing Autophagy via AKT/mTOR Pathway. J Cell Biochem 118:629-639
Khan, Nazir M; Haseeb, Abdul; Ansari, Mohammad Y et al. (2017) A wogonin-rich-fraction of Scutellaria baicalensis root extract exerts chondroprotective effects by suppressing IL-1?-induced activation of AP-1 in human OA chondrocytes. Sci Rep 7:43789
Makki, Mohammad S; Haqqi, Tariq M (2017) Histone deacetylase inhibitor vorinostat (SAHA, MK0683) perturb miR-9-MCPIP1 axis to block IL-1?-induced IL-6 expression in human OA chondrocytes. Connect Tissue Res 58:64-75
Magrey, Marina N; Haqqi, Tariq; Haseeb, Abdul (2016) Identification of plasma microRNA expression profile in radiographic axial spondyloarthritis-a pilot study. Clin Rheumatol 35:1323-7

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