microRNA-214-3p Suppresses Ankylosing Spondylitis Fibroblast Osteogenesis via BMP–TGFβ Axis and BMP2

Recent investigations suggest microRNAs (miRs) exert functions in fibroblast osteogenesis in ankylosing spondylitis (AS), an inflammatory rheumatic disease. But the mechanism of miR-214-3p in osteogenic differentiation in AS is not clearly understood yet. In this study, fibroblasts were obtained fro...

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Main Authors: Lixiang Ding, Yukun Yin, Yu Hou, Haoran Jiang, Ji Zhang, Zhong Dai, Genai Zhang
Format: Article
Language:English
Published: Frontiers Media S.A. 2021-04-01
Series:Frontiers in Endocrinology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fendo.2020.609753/full
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author Lixiang Ding
Yukun Yin
Yu Hou
Haoran Jiang
Ji Zhang
Zhong Dai
Genai Zhang
author_facet Lixiang Ding
Yukun Yin
Yu Hou
Haoran Jiang
Ji Zhang
Zhong Dai
Genai Zhang
author_sort Lixiang Ding
collection DOAJ
description Recent investigations suggest microRNAs (miRs) exert functions in fibroblast osteogenesis in ankylosing spondylitis (AS), an inflammatory rheumatic disease. But the mechanism of miR-214-3p in osteogenic differentiation in AS is not clearly understood yet. In this study, fibroblasts were obtained from the capsular ligament of patients with AS and femoral neck fracture and cultured for osteogenic induction and identified. The roles of miR-214-3p and bone morphogenic protein 2 (BMP2) in AS fibroblast osteogenesis were assessed via gain- and loss-of-function, alizarin red S staining, and alkaline phosphatase (ALP) detection. Levels of miR-214-3p, BMP2, osteogenic differentiation-related proteins, and BMP–TGFβ axis-related proteins were further measured. Consequently, miR-214-3p was downregulated in AS fibroblasts, with enhanced ALP activity and calcium nodules, which were reversed by miR-214-3p overexpression. BMP2 was a target gene of miR-214-3p and promoted AS fibroblast osteogenesis by activating BMP–TGFβ axis, while miR-214-3p inhibited AS fibroblast osteogenesis by targeting BMP2. Together, miR-214-3p could prevent AS fibroblast osteogenic differentiation by targeting BMP2 and blocking BMP–TGFβ axis. This study may offer a novel insight for AS treatment.
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spelling doaj.art-063e0f69aa76442d95de1d58d7e0e8a12022-12-21T22:45:18ZengFrontiers Media S.A.Frontiers in Endocrinology1664-23922021-04-011110.3389/fendo.2020.609753609753microRNA-214-3p Suppresses Ankylosing Spondylitis Fibroblast Osteogenesis via BMP–TGFβ Axis and BMP2Lixiang Ding0Yukun Yin1Yu Hou2Haoran Jiang3Ji Zhang4Zhong Dai5Genai Zhang6Department of Spine, Beijing Shijitan Hospital, Capital Medical University, Beijing, ChinaDepartment of Traditional Chinese Medicine, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, ChinaDepartment of Spine, Beijing Shijitan Hospital, Capital Medical University, Beijing, ChinaDepartment of Spine, Beijing Shijitan Hospital, Capital Medical University, Beijing, ChinaDepartment of Spine, Beijing Shijitan Hospital, Capital Medical University, Beijing, ChinaDepartment of General Medicine, Huanxing Cancer Hospital, Beijing, ChinaDepartment of Spine, Beijing Shijitan Hospital, Capital Medical University, Beijing, ChinaRecent investigations suggest microRNAs (miRs) exert functions in fibroblast osteogenesis in ankylosing spondylitis (AS), an inflammatory rheumatic disease. But the mechanism of miR-214-3p in osteogenic differentiation in AS is not clearly understood yet. In this study, fibroblasts were obtained from the capsular ligament of patients with AS and femoral neck fracture and cultured for osteogenic induction and identified. The roles of miR-214-3p and bone morphogenic protein 2 (BMP2) in AS fibroblast osteogenesis were assessed via gain- and loss-of-function, alizarin red S staining, and alkaline phosphatase (ALP) detection. Levels of miR-214-3p, BMP2, osteogenic differentiation-related proteins, and BMP–TGFβ axis-related proteins were further measured. Consequently, miR-214-3p was downregulated in AS fibroblasts, with enhanced ALP activity and calcium nodules, which were reversed by miR-214-3p overexpression. BMP2 was a target gene of miR-214-3p and promoted AS fibroblast osteogenesis by activating BMP–TGFβ axis, while miR-214-3p inhibited AS fibroblast osteogenesis by targeting BMP2. Together, miR-214-3p could prevent AS fibroblast osteogenic differentiation by targeting BMP2 and blocking BMP–TGFβ axis. This study may offer a novel insight for AS treatment.https://www.frontiersin.org/articles/10.3389/fendo.2020.609753/fullankylosing spondylitismicroRNA-214-3posteogenic differentiationbone morphogenic protein 2BMP–TGFβ signaling pathway
spellingShingle Lixiang Ding
Yukun Yin
Yu Hou
Haoran Jiang
Ji Zhang
Zhong Dai
Genai Zhang
microRNA-214-3p Suppresses Ankylosing Spondylitis Fibroblast Osteogenesis via BMP–TGFβ Axis and BMP2
Frontiers in Endocrinology
ankylosing spondylitis
microRNA-214-3p
osteogenic differentiation
bone morphogenic protein 2
BMP–TGFβ signaling pathway
title microRNA-214-3p Suppresses Ankylosing Spondylitis Fibroblast Osteogenesis via BMP–TGFβ Axis and BMP2
title_full microRNA-214-3p Suppresses Ankylosing Spondylitis Fibroblast Osteogenesis via BMP–TGFβ Axis and BMP2
title_fullStr microRNA-214-3p Suppresses Ankylosing Spondylitis Fibroblast Osteogenesis via BMP–TGFβ Axis and BMP2
title_full_unstemmed microRNA-214-3p Suppresses Ankylosing Spondylitis Fibroblast Osteogenesis via BMP–TGFβ Axis and BMP2
title_short microRNA-214-3p Suppresses Ankylosing Spondylitis Fibroblast Osteogenesis via BMP–TGFβ Axis and BMP2
title_sort microrna 214 3p suppresses ankylosing spondylitis fibroblast osteogenesis via bmp tgfβ axis and bmp2
topic ankylosing spondylitis
microRNA-214-3p
osteogenic differentiation
bone morphogenic protein 2
BMP–TGFβ signaling pathway
url https://www.frontiersin.org/articles/10.3389/fendo.2020.609753/full
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