Circ_0006646 Promotes the Progression of Osteoarthritis via Upregulating CDH11 Expression in an IGF2BP2‐Dependent Manner

ABSTRACT Osteoarthritis (OA) is a common degenerative osteoarthropathy with an unclear pathogenesis. Circular RNA (circRNA) has been reported to be associated with OA progression. This study aims to explore the role and potential mechanism of hsa_circ_0006646 in OA. Interleukin‐1β (IL‐1β)‐induced hu...

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Main Authors: Ming‐Yu Hua, Guo‐Liang Wang, Wen‐Hao Duan, Xiao‐Heng Tang
Format: Article
Language:English
Published: Wiley 2025-08-01
Series:Kaohsiung Journal of Medical Sciences
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Online Access:https://doi.org/10.1002/kjm2.70031
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author Ming‐Yu Hua
Guo‐Liang Wang
Wen‐Hao Duan
Xiao‐Heng Tang
author_facet Ming‐Yu Hua
Guo‐Liang Wang
Wen‐Hao Duan
Xiao‐Heng Tang
author_sort Ming‐Yu Hua
collection DOAJ
description ABSTRACT Osteoarthritis (OA) is a common degenerative osteoarthropathy with an unclear pathogenesis. Circular RNA (circRNA) has been reported to be associated with OA progression. This study aims to explore the role and potential mechanism of hsa_circ_0006646 in OA. Interleukin‐1β (IL‐1β)‐induced human chondrocytes were used as the cell model of OA. RT‐qPCR and western blotting were used to detect the expression of circ_0006646, IGF2BP2, and cadherin 11 (CDH11). Cell counting kit‐8 assay, 5‐ethynyl‐2′‐deoxyuridine assay, and flow cytometry were performed to assess chondrocyte cell proliferation and apoptosis, respectively. Western blot assay was performed to determine the levels of proliferation‐related proteins, apoptosis‐related proteins, and extracellular matrix (ECM) proteins. RNA immunoprecipitation (RIP) assay was performed to verify the interaction between IGF2BP2 and circ_0006646 or CDH11. In OA patients and IL‐1β‐stimulated chondrocytes, circ_0006646 and CDH11 were upregulated. IL‐1β suppressed proliferation and induced apoptosis, inflammation, and ECM degradation in chondrocytes, and circ_0006646 knockdown protected chondrocytes from IL‐1β‐induced damage. IGF2BP2 was proved to interact with both circ_0006646 and CDH11. The overexpression of IGF2BP2 or CDH11 enhanced IL‐1β‐induced apoptosis, inflammation, and ECM degradation in chondrocytes. Moreover, circ_0006646 absence‐mediated effects in IL‐1β‐treated chondrocytes could be largely overturned by the overexpression of IGF2BP2 or CDH11. In conclusion, circ_0006646 knockdown protected chondrocytes from IL‐1β‐induced injury by regulating CDH11 in an IGF2BP2‐dependent manner, suggesting a novel potential target for OA treatment.
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spelling doaj-art-165a1afc6ef6408b9334bcc1a6fa84db2025-08-21T04:28:12ZengWileyKaohsiung Journal of Medical Sciences1607-551X2410-86502025-08-01418n/an/a10.1002/kjm2.70031Circ_0006646 Promotes the Progression of Osteoarthritis via Upregulating CDH11 Expression in an IGF2BP2‐Dependent MannerMing‐Yu Hua0Guo‐Liang Wang1Wen‐Hao Duan2Xiao‐Heng Tang3Department of Orthopaedics Tangdu Hospital, Fourth Military Medical University Xi'an Shaanxi ChinaDepartment of Orthopaedics Tangdu Hospital, Fourth Military Medical University Xi'an Shaanxi ChinaDepartment of Orthopaedics Xi'an Medical University Xi'an Shaanxi ChinaDepartment of Orthopaedics Tangdu Hospital, Fourth Military Medical University Xi'an Shaanxi ChinaABSTRACT Osteoarthritis (OA) is a common degenerative osteoarthropathy with an unclear pathogenesis. Circular RNA (circRNA) has been reported to be associated with OA progression. This study aims to explore the role and potential mechanism of hsa_circ_0006646 in OA. Interleukin‐1β (IL‐1β)‐induced human chondrocytes were used as the cell model of OA. RT‐qPCR and western blotting were used to detect the expression of circ_0006646, IGF2BP2, and cadherin 11 (CDH11). Cell counting kit‐8 assay, 5‐ethynyl‐2′‐deoxyuridine assay, and flow cytometry were performed to assess chondrocyte cell proliferation and apoptosis, respectively. Western blot assay was performed to determine the levels of proliferation‐related proteins, apoptosis‐related proteins, and extracellular matrix (ECM) proteins. RNA immunoprecipitation (RIP) assay was performed to verify the interaction between IGF2BP2 and circ_0006646 or CDH11. In OA patients and IL‐1β‐stimulated chondrocytes, circ_0006646 and CDH11 were upregulated. IL‐1β suppressed proliferation and induced apoptosis, inflammation, and ECM degradation in chondrocytes, and circ_0006646 knockdown protected chondrocytes from IL‐1β‐induced damage. IGF2BP2 was proved to interact with both circ_0006646 and CDH11. The overexpression of IGF2BP2 or CDH11 enhanced IL‐1β‐induced apoptosis, inflammation, and ECM degradation in chondrocytes. Moreover, circ_0006646 absence‐mediated effects in IL‐1β‐treated chondrocytes could be largely overturned by the overexpression of IGF2BP2 or CDH11. In conclusion, circ_0006646 knockdown protected chondrocytes from IL‐1β‐induced injury by regulating CDH11 in an IGF2BP2‐dependent manner, suggesting a novel potential target for OA treatment.https://doi.org/10.1002/kjm2.70031CDH11chondrocytecirc_0006646IGF2BP2osteoarthritis
spellingShingle Ming‐Yu Hua
Guo‐Liang Wang
Wen‐Hao Duan
Xiao‐Heng Tang
Circ_0006646 Promotes the Progression of Osteoarthritis via Upregulating CDH11 Expression in an IGF2BP2‐Dependent Manner
Kaohsiung Journal of Medical Sciences
CDH11
chondrocyte
circ_0006646
IGF2BP2
osteoarthritis
title Circ_0006646 Promotes the Progression of Osteoarthritis via Upregulating CDH11 Expression in an IGF2BP2‐Dependent Manner
title_full Circ_0006646 Promotes the Progression of Osteoarthritis via Upregulating CDH11 Expression in an IGF2BP2‐Dependent Manner
title_fullStr Circ_0006646 Promotes the Progression of Osteoarthritis via Upregulating CDH11 Expression in an IGF2BP2‐Dependent Manner
title_full_unstemmed Circ_0006646 Promotes the Progression of Osteoarthritis via Upregulating CDH11 Expression in an IGF2BP2‐Dependent Manner
title_short Circ_0006646 Promotes the Progression of Osteoarthritis via Upregulating CDH11 Expression in an IGF2BP2‐Dependent Manner
title_sort circ 0006646 promotes the progression of osteoarthritis via upregulating cdh11 expression in an igf2bp2 dependent manner
topic CDH11
chondrocyte
circ_0006646
IGF2BP2
osteoarthritis
url https://doi.org/10.1002/kjm2.70031
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AT wenhaoduan circ0006646promotestheprogressionofosteoarthritisviaupregulatingcdh11expressioninanigf2bp2dependentmanner
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