PMID- 36401176
OWN - NLM
STAT- MEDLINE
DCOM- 20221122
LR  - 20221130
IS  - 1528-3658 (Electronic)
IS  - 1076-1551 (Print)
IS  - 1076-1551 (Linking)
VI  - 28
IP  - 1
DP  - 2022 Nov 18
TI  - CircRNA AFF4 induced by KDM1A promotes osteogenic differentiation through 
      FNDC5/Irisin pathway.
PG  - 134
LID - 10.1186/s10020-022-00557-7 [doi]
LID - 134
AB  - 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.
CI  - (c) 2022. The Author(s).
FAU - Liu, Ansong
AU  - Liu A
AD  - The First Affiliated Hospital, Department of Orthopedics, Hengyang Medical 
      School, University of South China, No. 69 Chuanshan Road, Hengyang, Hunan, 
      421001, China.
FAU - Chen, Yong
AU  - Chen Y
AD  - The First Affiliated Hospital, Department of Spine, Hengyang Medical School, 
      University of South China, No. 69 Chuanshan Road, Hengyang, Hunan, 421001, China.
FAU - Zhong, Da
AU  - Zhong D
AD  - Department of Orthopedics, Xiangya Hospital, Central South University, No.87 
      Xiangya Road, 410008, Changsha, Hunan, China.
FAU - Wang, Chenggong
AU  - Wang C
AD  - Department of Orthopedics, Xiangya Hospital, Central South University, No.87 
      Xiangya Road, 410008, Changsha, Hunan, China.
FAU - Yu, Mi
AU  - Yu M
AD  - Hengyang Medical School, University of South China, Hengyang, Hunan, 421001, 
      China.
FAU - Liu, Chao
AU  - Liu C
AD  - The First Affiliated Hospital, Department of Orthopedics, Hengyang Medical 
      School, University of South China, No. 69 Chuanshan Road, Hengyang, Hunan, 
      421001, China.
FAU - Yang, Zhijun
AU  - Yang Z
AD  - The First Affiliated Hospital, Department of Orthopedics, Hengyang Medical 
      School, University of South China, No. 69 Chuanshan Road, Hengyang, Hunan, 
      421001, China.
FAU - Chen, Wenkang
AU  - Chen W
AD  - The First Affiliated Hospital, Department of Orthopedics, Hengyang Medical 
      School, University of South China, No. 69 Chuanshan Road, Hengyang, Hunan, 
      421001, China.
FAU - Yin, Ke
AU  - Yin K
AUID- ORCID: 0000-0002-8196-1377
AD  - 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.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20221118
PL  - England
TA  - Mol Med
JT  - Molecular medicine (Cambridge, Mass.)
JID - 9501023
RN  - 0 (RNA, Circular)
RN  - 0 (Fibronectins)
RN  - 0 (Transcription Factors)
RN  - 0 (FNDC5 protein, mouse)
SB  - IM
MH  - Mice
MH  - Animals
MH  - *RNA, Circular/genetics
MH  - *Osteogenesis/genetics
MH  - Fibronectins/genetics
MH  - In Situ Hybridization, Fluorescence
MH  - Transcription Factors/genetics
PMC - PMC9673395
OTO - NOTNLM
OT  - Circular RNA AFF4
OT  - FNDC5
OT  - Irisin
OT  - KDM1A
OT  - Osteogenic differentiation
COIS- No conflicts of interest, financial or otherwise, are declared by the authors.
EDAT- 2022/11/20 06:00
MHDA- 2022/11/23 06:00
PMCR- 2022/11/18
CRDT- 2022/11/19 00:02
PHST- 2022/06/10 00:00 [received]
PHST- 2022/10/13 00:00 [accepted]
PHST- 2022/10/08 00:00 [revised]
PHST- 2022/11/19 00:02 [entrez]
PHST- 2022/11/20 06:00 [pubmed]
PHST- 2022/11/23 06:00 [medline]
PHST- 2022/11/18 00:00 [pmc-release]
AID - 10.1186/s10020-022-00557-7 [pii]
AID - 557 [pii]
AID - 10.1186/s10020-022-00557-7 [doi]
PST - epublish
SO  - Mol Med. 2022 Nov 18;28(1):134. doi: 10.1186/s10020-022-00557-7.