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CircRNA AFF4 induced by KDM1A promotes osteogenic differentiation through FNDC5/Irisin pathway.
Liu, Ansong; Chen, Yong; Zhong, Da; Wang, Chenggong; Yu, Mi; Liu, Chao; Yang, Zhijun; Chen, Wenkang; Yin, Ke.
Afiliación
  • Liu A; The First Affiliated Hospital, Department of Orthopedics, Hengyang Medical School, University of South China, No. 69 Chuanshan Road, Hengyang, Hunan, 421001, China.
  • Chen Y; The First Affiliated Hospital, Department of Spine, Hengyang Medical School, University of South China, No. 69 Chuanshan Road, Hengyang, Hunan, 421001, China.
  • Zhong D; Department of Orthopedics, Xiangya Hospital, Central South University, No.87 Xiangya Road, 410008, Changsha, Hunan, China.
  • Wang C; Department of Orthopedics, Xiangya Hospital, Central South University, No.87 Xiangya Road, 410008, Changsha, Hunan, China.
  • Yu M; Hengyang Medical School, University of South China, Hengyang, Hunan, 421001, China.
  • Liu C; The First Affiliated Hospital, Department of Orthopedics, Hengyang Medical School, University of South China, No. 69 Chuanshan Road, Hengyang, Hunan, 421001, China.
  • Yang Z; The First Affiliated Hospital, Department of Orthopedics, Hengyang Medical School, University of South China, No. 69 Chuanshan Road, Hengyang, Hunan, 421001, China.
  • Chen W; The First Affiliated Hospital, Department of Orthopedics, Hengyang Medical School, University of South China, No. 69 Chuanshan Road, Hengyang, Hunan, 421001, China.
  • Yin K; The First Affiliated Hospital, Department of Orthopedics, Hengyang Medical School, University of South China, No. 69 Chuanshan Road, Hengyang, Hunan, 421001, China. ink2000_2000@sina.com.
Mol Med ; 28(1): 134, 2022 11 18.
Article en En | MEDLINE | ID: mdl-36401176
ABSTRACT

BACKGROUND:

Circular RNA (circ) AFF4 was documented to regulate osteogenesis but the underlying mechanism remains to be elucidated. The preliminary study showed that circ_AFF4 may promote osteogenesis via FNDC5/Irisin. Furthermore, the online prediction tool indicated the interaction of circ_AFF4, insulin-like growth factor-2 mRNA-binding protein 3 (IGF2BP3), FNDC5 and lysine (K)-specific demethylase 1 A (KDM1A). Therefore, this study aims to elucidate the relationships of KDM1A, circ_AFF4, IGF2BP3 and FNDC5/Irisin during osteogenesis.

METHODS:

The alkaline phosphatase (ALP) activities and osteogenic-related factors were determined using ALP and alizarin red S (ARS) staining, real-time quantitative PCR(RT-qPCR) and western blot. Immunoprecipitation (RIP), pull-down assay and fluorescence in situ hybridization (FISH) were used to examine the interactions among circ_AFF4/IGF2BP3/FNDC5. A mouse in vivo model was utilized to further confirm the regulatory effect on bone formation.

RESULTS:

Circ_AFF4 and KDM1A expression levels were increased during osteoinduction of BM-MSCs. Knockdown of circ_AFF4 and KDM1A significantly suppressed BM-MSC osteogenesis. We also proved that KDM1A directly bound to circ_AFF4 and FNDC5 promoter and induced circ_AFF4 and FNDC5 expression. Furthermore, circ_AFF4 enhanced the stability of FNDC5 by generating a circ_AFF4, IGF2BP3 and FNDC5 RNA-protein complex, and thereby induced Irisin and osteogenesis. The in vitro data was confirmed with in vivo model.

CONCLUSION:

These findings elucidate that KDM1A induces circ_AFF4, which promotes promote osteogenesis via IGF2BP3. This study indicates that circ_AFF4 may potentially represent a critical therapeutic target for the diseases.
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Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Osteogénesis / ARN Circular Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: Mol Med Asunto de la revista: BIOLOGIA MOLECULAR Año: 2022 Tipo del documento: Article País de afiliación: China
Texto completo
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Osteogénesis / ARN Circular Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: Mol Med Asunto de la revista: BIOLOGIA MOLECULAR Año: 2022 Tipo del documento: Article País de afiliación: China