Higher expression of whole blood microRNA-21 in patients with ankylosing spondylitis associated with programmed cell death 4 mRNA expression and collagen cross-linked C-telopeptide concentration.
OBJECTIVE
Bone loss is a recognized feature of ankylosing spondylitis (AS). The binding of microRNA-21 (miR-21) to programmed cell death 4 (PDCD4) could inhibit the expression of PDCD4 and further induce the activation of osteoclasts. In the present study, we compared the difference in miR-21 expression between patients with AS and healthy controls, and evaluated the relationships of miR-21, PDCD4 mRNA, and bone erosion in patients with AS. The influences of nonsteroidal antiinflammatory drugs (NSAID) and disease-modifying antirheumatic drugs (DMARD) on the expressions of miR-21 and PDCD4 mRNA in patients with AS were also assessed.


METHODS
Whole blood miR-21 and PDCD4 mRNA expression were evaluated by quantitative real-time PCR among 122 patients with AS and 122 healthy controls. The serum level of collagen cross-linked C-telopeptide (CTX) was measured using ELISA.


RESULTS
When compared to controls, patients with AS had significantly higher levels of miR-21, PDCD4 mRNA, and CTX. MiR-21 expression was negatively correlated with PDCD4 mRNA expression in patients with AS who were taking neither NSAID nor DMARD. Interestingly, significantly positive correlations between miR-21 expression with PDCD4 mRNA expression (r = 0.33, p = 0.01) and CTX level (r = 0.44, p < 0.01) were observed in patients with AS who were taking sulfasalazine. Positive correlations of miR-21 and CTX level were also observed in AS patients with disease duration < 7.0 years (r = 0.36, p = 0.004) and active disease (r = 0.42, p = 0.001).


CONCLUSIONS
The expression of miR-21 might have a role in the development of AS.
From the Institute of Medicine, Department of Public Health, Chung Shan Medical University; Division of Allergy, Immunology and Rheumatology, Department of Family and Community Medicine, Chung Shan Medical University Hospital, Taichung; Department of Clinical Pharmacy, Taipei Medical University; Department of Pharmacy, Taipei Medical University-Wanfang Hospital, Taipei, Taiwan.C-H. Huang, MSc; J.C-C. Wei, MD, PhD, Institute of Medicine, Division of Allergy, Immunology and Rheumatology, Chung Shan Medical University Hospital; S-Y. Chiou, BSc; C-H. Chou, BSc; Y-J. Lin, BSc; P-H. Hung, BSc; R-H. Wong, PhD, Department of Public Health, Chung Shan Medical University, and Department of Family and Community Medicine, Chung Shan Medical University Hospital; W-C. Chang, PhD, Department of Clinical Pharmacy, Taipei Medical University, and Department of Pharmacy, Taipei Medical University-Wanfang Hospital.
Chun-Huang
CH
Huang
From the Institute of Medicine, Department of Public Health, Chung Shan Medical University; Division of Allergy, Immunology and Rheumatology, Department of Family and Community Medicine, Chung Shan Medical University Hospital, Taichung; Department of Clinical Pharmacy, Taipei Medical University; Department of Pharmacy, Taipei Medical University-Wanfang Hospital, Taipei, Taiwan.C-H. Huang, MSc; J.C-C. Wei, MD, PhD, Institute of Medicine, Division of Allergy, Immunology and Rheumatology, Chung Shan Medical University Hospital; S-Y. Chiou, BSc; C-H. Chou, BSc; Y-J. Lin, BSc; P-H. Hung, BSc; R-H. Wong, PhD, Department of Public Health, Chung Shan Medical University, and Department of Family and Community Medicine, Chung Shan Medical University Hospital; W-C. Chang, PhD, Department of Clinical Pharmacy, Taipei Medical University, and Department of Pharmacy, Taipei Medical University-Wanfang Hospital.
James Cheng-Chung
JC
Wei
From the Institute of Medicine, Department of Public Health, Chung Shan Medical University; Division of Allergy, Immunology and Rheumatology, Department of Family and Community Medicine, Chung Shan Medical University Hospital, Taichung; Department of Clinical Pharmacy, Taipei Medical University; Department of Pharmacy, Taipei Medical University-Wanfang Hospital, Taipei, Taiwan.C-H. Huang, MSc; J.C-C. Wei, MD, PhD, Institute of Medicine, Division of Allergy, Immunology and Rheumatology, Chung Shan Medical University Hospital; S-Y. Chiou, BSc; C-H. Chou, BSc; Y-J. Lin, BSc; P-H. Hung, BSc; R-H. Wong, PhD, Department of Public Health, Chung Shan Medical University, and Department of Family and Community Medicine, Chung Shan Medical University Hospital; W-C. Chang, PhD, Department of Clinical Pharmacy, Taipei Medical University, and Department of Pharmacy, Taipei Medical University-Wanfang Hospital.
Wei-Chiao
WC
Chang
From the Institute of Medicine, Department of Public Health, Chung Shan Medical University; Division of Allergy, Immunology and Rheumatology, Department of Family and Community Medicine, Chung Shan Medical University Hospital, Taichung; Department of Clinical Pharmacy, Taipei Medical University; Department of Pharmacy, Taipei Medical University-Wanfang Hospital, Taipei, Taiwan.C-H. Huang, MSc; J.C-C. Wei, MD, PhD, Institute of Medicine, Division of Allergy, Immunology and Rheumatology, Chung Shan Medical University Hospital; S-Y. Chiou, BSc; C-H. Chou, BSc; Y-J. Lin, BSc; P-H. Hung, BSc; R-H. Wong, PhD, Department of Public Health, Chung Shan Medical University, and Department of Family and Community Medicine, Chung Shan Medical University Hospital; W-C. Chang, PhD, Department of Clinical Pharmacy, Taipei Medical University, and Department of Pharmacy, Taipei Medical University-Wanfang Hospital.
Shang-Yan
SY
Chiou
From the Institute of Medicine, Department of Public Health, Chung Shan Medical University; Division of Allergy, Immunology and Rheumatology, Department of Family and Community Medicine, Chung Shan Medical University Hospital, Taichung; Department of Clinical Pharmacy, Taipei Medical University; Department of Pharmacy, Taipei Medical University-Wanfang Hospital, Taipei, Taiwan.C-H. Huang, MSc; J.C-C. Wei, MD, PhD, Institute of Medicine, Division of Allergy, Immunology and Rheumatology, Chung Shan Medical University Hospital; S-Y. Chiou, BSc; C-H. Chou, BSc; Y-J. Lin, BSc; P-H. Hung, BSc; R-H. Wong, PhD, Department of Public Health, Chung Shan Medical University, and Department of Family and Community Medicine, Chung Shan Medical University Hospital; W-C. Chang, PhD, Department of Clinical Pharmacy, Taipei Medical University, and Department of Pharmacy, Taipei Medical University-Wanfang Hospital.
Chia-Hsuan
CH
Chou
From the Institute of Medicine, Department of Public Health, Chung Shan Medical University; Division of Allergy, Immunology and Rheumatology, Department of Family and Community Medicine, Chung Shan Medical University Hospital, Taichung; Department of Clinical Pharmacy, Taipei Medical University; Department of Pharmacy, Taipei Medical University-Wanfang Hospital, Taipei, Taiwan.C-H. Huang, MSc; J.C-C. Wei, MD, PhD, Institute of Medicine, Division of Allergy, Immunology and Rheumatology, Chung Shan Medical University Hospital; S-Y. Chiou, BSc; C-H. Chou, BSc; Y-J. Lin, BSc; P-H. Hung, BSc; R-H. Wong, PhD, Department of Public Health, Chung Shan Medical University, and Department of Family and Community Medicine, Chung Shan Medical University Hospital; W-C. Chang, PhD, Department of Clinical Pharmacy, Taipei Medical University, and Department of Pharmacy, Taipei Medical University-Wanfang Hospital.
Yu-Jie
YJ
Lin
From the Institute of Medicine, Department of Public Health, Chung Shan Medical University; Division of Allergy, Immunology and Rheumatology, Department of Family and Community Medicine, Chung Shan Medical University Hospital, Taichung; Department of Clinical Pharmacy, Taipei Medical University; Department of Pharmacy, Taipei Medical University-Wanfang Hospital, Taipei, Taiwan.C-H. Huang, MSc; J.C-C. Wei, MD, PhD, Institute of Medicine, Division of Allergy, Immunology and Rheumatology, Chung Shan Medical University Hospital; S-Y. Chiou, BSc; C-H. Chou, BSc; Y-J. Lin, BSc; P-H. Hung, BSc; R-H. Wong, PhD, Department of Public Health, Chung Shan Medical University, and Department of Family and Community Medicine, Chung Shan Medical University Hospital; W-C. Chang, PhD, Department of Clinical Pharmacy, Taipei Medical University, and Department of Pharmacy, Taipei Medical University-Wanfang Hospital.
Pei-Hsuan
PH
Hung
From the Institute of Medicine, Department of Public Health, Chung Shan Medical University; Division of Allergy, Immunology and Rheumatology, Department of Family and Community Medicine, Chung Shan Medical University Hospital, Taichung; Department of Clinical Pharmacy, Taipei Medical University; Department of Pharmacy, Taipei Medical University-Wanfang Hospital, Taipei, Taiwan.C-H. Huang, MSc; J.C-C. Wei, MD, PhD, Institute of Medicine, Division of Allergy, Immunology and Rheumatology, Chung Shan Medical University Hospital; S-Y. Chiou, BSc; C-H. Chou, BSc; Y-J. Lin, BSc; P-H. Hung, BSc; R-H. Wong, PhD, Department of Public Health, Chung Shan Medical University, and Department of Family and Community Medicine, Chung Shan Medical University Hospital; W-C. Chang, PhD, Department of Clinical Pharmacy, Taipei Medical University, and Department of Pharmacy, Taipei Medical University-Wanfang Hospital. rueyhong@csmu.edu.tw.
Ruey-Hong
RH
Wong
D000293:Adolescent; D000328:Adult; D000368:Aged; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use; D018501:Antirheumatic Agents / Q000627:therapeutic use; D051017:Apoptosis Regulatory Proteins / Q000097:blood* / Q000235:genetics; D024042:Collagen Type I / Q000097:blood* / Q000235:genetics; D005260:Female; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000097:blood* / Q000235:genetics; D008875:Middle Aged; D010455:Peptides / Q000097:blood* / Q000235:genetics; D012333:RNA, Messenger; D016601:RNA-Binding Proteins / Q000097:blood* / Q000235:genetics; D013167:Spondylitis, Ankylosing / Q000097:blood* / Q000188:drug therapy; D055815:Young Adult
D000894:Anti-Inflammatory Agents, Non-Steroidal; D018501:Antirheumatic Agents; D051017:Apoptosis Regulatory Proteins; D024042:Collagen Type I; C524940:MIRN21 microRNA, human; D035683:MicroRNAs; C114487:PDCD4 protein, human; D010455:Peptides; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; C052929:collagen type I trimeric cross-linked peptide
ANKYLOSING SPONDYLITIS; COLLAGEN CROSS-LINKED C-TELOPEPTIDE; MICRORNA-21; PROGRAMMED CELL DEATH 4