Title:miR-18a-3p Encourages Apoptosis of Chondrocyte in Osteoarthritis via HOXA1 Pathway
VOLUME: 13 ISSUE: 4
Author(s):Baiyang Ding, Shujuan Xu, Xiumin Sun, Jianming Gao, Wenlei Nie and Hongguang Xu *
Affiliation:Spine Research Center of Wannan Medical College, Key Laboratory of Non-coding RNA Transformation Research of Anhui Higher Education Institution, Department of Spine Surgery, Yijishan hospital of Wannan Medical College, Wuhu, Anhui 241001, Spine Research Center of Wannan Medical College, Key Laboratory of Non-coding RNA Transformation Research of Anhui Higher Education Institution, Department of Spine Surgery, Yijishan hospital of Wannan Medical College, Wuhu, Anhui 241001, Spine Research Center of Wannan Medical College, Key Laboratory of Non-coding RNA Transformation Research of Anhui Higher Education Institution, Department of Spine Surgery, Yijishan hospital of Wannan Medical College, Wuhu, Anhui 241001, Spine Research Center of Wannan Medical College, Key Laboratory of Non-coding RNA Transformation Research of Anhui Higher Education Institution, Department of Spine Surgery, Yijishan hospital of Wannan Medical College, Wuhu, Anhui 241001, Spine Research Center of Wannan Medical College, Key Laboratory of Non-coding RNA Transformation Research of Anhui Higher Education Institution, Department of Spine Surgery, Yijishan hospital of Wannan Medical College, Wuhu, Anhui 241001, Spine Research Center of Wannan Medical College, Key Laboratory of Non-coding RNA Transformation Research of Anhui Higher Education Institution, Department of Spine Surgery, Yijishan hospital of Wannan Medical College, Wuhu, Anhui 241001
Keywords:Osteoarthritis, miR-18a-3p, HOXA-1, IL-1β, chondrocytes, chemical analysis.
Abstract:
Background: Osteoarthritis is a disorder of joints featuring inflammation and degeneration
of articular cartilage. Recently, miRs have been found to be associated in the regulation of chondrocytes
and their apoptosis. miR-18a-3p has been found to be associated in the pathogenesis of rheumatoid
arthritis, however, its role in articular cartilage tissues remains unclear.
Methods: C57BL/6 strain of mice and human cartilage tissue were used for the study. Histological
analysis was done on isolated cartilage samples followed by TUNEL assay and immunohistochemical
analysis. The chondrocytes were isolated from mouse and human cartilage tissues, RNA was isolated
and subjected for qRT-PCR analysis. The chondrocytes were transfected with miR-18a-3p agomir,
antagomir and siHOXA-1. Luciferase assay was done in 293T cells. Flow cytometry analysis was
done and western blot analysis for studying the expression of proteins.
Results: The expression of miR-18a-3p was upregulated in chondrocytes after exposing them to interlukin-
1β (IL-1β) in vitro. The transfection of miR-18a-3p antagomir halted the IL-1β mediated apoptosis.
The luciferase assay suggested that miR-18a-3p targets the 3’UTR region of HOXA1 gene thus
blocking its expression. The treatment of HOXA1 siRNA demonstrated the rescuing effect of miR-
18a-3p antagomir on the apoptosis of chondrocytes. Treatment of miR-18a-3p antagomir attenuated
the surface of cartilage in osteoarthritis mice and the agomir worsened it. TUNEL assay suggested
decreased apoptosis and over-expression of HOAX1 in osteoarthritis mice post miR-18a-3p knockdown.
Conclusion: The findings confirmed the involvement of miR-18a-3p/HOXA1 pathway as a potential
mechanism in the regulation of Osteoarthritis.
