PMID- 37434265
OWN - NLM
STAT- MEDLINE
DCOM- 20230713
LR  - 20230718
IS  - 1749-799X (Electronic)
IS  - 1749-799X (Linking)
VI  - 18
IP  - 1
DP  - 2023 Jul 11
TI  - CircZNF367 promotes osteoclast differentiation and osteoporosis by interacting 
      with FUS to maintain CRY2 mRNA stability.
PG  - 492
LID - 10.1186/s13018-023-03955-7 [doi]
LID - 492
AB  - BACKGROUND: Osteoporosis, characterized by reduced bone mass and deterioration of 
      bone quality, is a significant health concern for postmenopausal women. 
      Considering that the specific role of circRNAs in osteoporosis and osteoclast 
      differentiation remains poorly understood, this study aims to shed light on their 
      involvement in these processes to enhance our understanding and potentially 
      contribute to improved treatment strategies for osteoporosis. METHODS: An 
      osteoporotic model was constructed in vivo in ovariectomized mouse. In vitro, we 
      induced osteoclast formation in bone marrow-derived macrophages (BMDMs) using 
      M-CSF + RANKL. To assess osteoporosis in mice, we conducted HE staining. We used 
      MTT and TRAP staining to measure cell viability and osteoclast formation, 
      respectively, and also evaluated their mRNA and protein expression levels. In 
      addition, RNA pull-down, RIP and luciferase reporter assays were performed to 
      investigate interactions, and ChIP assay was used to examine the impact of 
      circZNF367 knockdown on the binding between FUS and CRY2. RESULTS: We observed 
      increased expression of CircZNF367, FUS and CRY2 in osteoporotic mice and 
      M-CSF + RANKL-induced BMDMs. Functionally, knocking down circZNF367 inhibited 
      osteoporosis in vivo. Furthermore, interference with circZNF367 suppressed 
      osteoclast proliferation and the expression of TRAP, NFATc1, and c-FOS. 
      Mechanistically, circZNF367 interacted with FUS to maintain CRY2 mRNA stability. 
      Additionally, knocking down CRY2 rescued M-CSF + RANKL-induced osteoclast 
      differentiation in BMDMs promoted by circZNF367 and FUS. CONCLUSION: This study 
      reveals that the circZNF367/FUS axis may accelerate osteoclasts differentiation 
      by upregulating CRY2 in osteoporosis and suggests that targeting circZNF367 may 
      have potential therapeutic effects on osteoporosis.
CI  - (c) 2023. The Author(s).
FAU - Deng, Mingsi
AU  - Deng M
AD  - Department of Stomatology, The Third Xiangya Hospital of Central South 
      University, Changsha, 410013, Hunan, People's Republic of China.
AD  - Department of Orthodontics, Changsha Stomatology Hospital, Changsha, 410005, 
      Hunan, People's Republic of China.
FAU - Wang, Zhengguang
AU  - Wang Z
AD  - Department of Spine Surgery, The Third Xiangya Hospital of Central South 
      University, Changsha, 410013, Hunan, People's Republic of China.
FAU - Luo, Jia
AU  - Luo J
AD  - Changsha Blood Center, Changsha, 410001, Hunan, People's Republic of China.
FAU - Cao, Heng
AU  - Cao H
AD  - The Department of Wound Joint Surgery, Affiliated Hospital of Yiyang Medical 
      College, Yiyang, 413000, Hunan, People's Republic of China.
FAU - Li, Yong
AU  - Li Y
AD  - Department of Emergency, The Third Xiangya Hospital of Central South University, 
      Changsha, 410013, Hunan, People's Republic of China.
FAU - Chen, Liangjian
AU  - Chen L
AD  - Department of Stomatology, The Third Xiangya Hospital of Central South 
      University, Changsha, 410013, Hunan, People's Republic of China.
FAU - Liu, Gengyan
AU  - Liu G
AD  - Department of Orthopedics, The Third Xiangya Hospital, Central South University, 
      No.138, Tongzipo Road, Yuelu District, Changsha, 410013, Hunan, People's Republic 
      of China. liugengyan1102@163.com.
LA  - eng
PT  - Journal Article
DEP - 20230711
PL  - England
TA  - J Orthop Surg Res
JT  - Journal of orthopaedic surgery and research
JID - 101265112
RN  - 81627-83-0 (Macrophage Colony-Stimulating Factor)
RN  - 0 (RNA, Circular)
RN  - 0 (FUS protein, mouse)
RN  - 0 (Cry2 protein, mouse)
SB  - IM
MH  - Animals
MH  - Female
MH  - Mice
MH  - Cell Differentiation/genetics
MH  - Macrophage Colony-Stimulating Factor
MH  - Osteoclasts
MH  - *Osteoporosis/genetics
MH  - RNA Stability/genetics
MH  - *RNA, Circular/genetics
PMC - PMC10334599
OTO - NOTNLM
OT  - CRY2
OT  - CircZNF367
OT  - FUS
OT  - Osteoclast differentiation
OT  - Osteoporosis
COIS- The authors declare no competing interests.
EDAT- 2023/07/12 01:07
MHDA- 2023/07/13 06:42
PMCR- 2023/07/11
CRDT- 2023/07/11 23:47
PHST- 2023/02/16 00:00 [received]
PHST- 2023/06/23 00:00 [accepted]
PHST- 2023/07/13 06:42 [medline]
PHST- 2023/07/12 01:07 [pubmed]
PHST- 2023/07/11 23:47 [entrez]
PHST- 2023/07/11 00:00 [pmc-release]
AID - 10.1186/s13018-023-03955-7 [pii]
AID - 3955 [pii]
AID - 10.1186/s13018-023-03955-7 [doi]
PST - epublish
SO  - J Orthop Surg Res. 2023 Jul 11;18(1):492. doi: 10.1186/s13018-023-03955-7.