PMID- 37884520
OWN - NLM
STAT- MEDLINE
DCOM- 20231115
LR  - 20231115
IS  - 2095-4700 (Print)
IS  - 2095-6231 (Electronic)
IS  - 2095-4700 (Linking)
VI  - 11
IP  - 1
DP  - 2023 Oct 26
TI  - Trim21 depletion alleviates bone loss in osteoporosis via activation of 
      YAP1/beta-catenin signaling.
PG  - 56
LID - 10.1038/s41413-023-00296-3 [doi]
LID - 56
AB  - Despite the diverse roles of tripartite motif (Trim)-containing proteins in the 
      regulation of autophagy, the innate immune response, and cell differentiation, 
      their roles in skeletal diseases are largely unknown. We recently demonstrated 
      that Trim21 plays a crucial role in regulating osteoblast (OB) differentiation in 
      osteosarcoma. However, how Trim21 contributes to skeletal degenerative disorders, 
      including osteoporosis, remains unknown. First, human and mouse bone specimens 
      were evaluated, and the results showed that Trim21 expression was significantly 
      elevated in bone tissues obtained from osteoporosis patients. Next, we found that 
      global knockout of the Trim21 gene (KO, Trim21(-/-)) resulted in higher bone mass 
      compared to that of the control littermates. We further demonstrated that loss of 
      Trim21 promoted bone formation by enhancing the osteogenic differentiation of 
      bone marrow mesenchymal stem cells (BMSCs) and elevating the activity of OBs; 
      moreover, Trim21 depletion suppressed osteoclast (OC) formation of RAW264.7 
      cells. In addition, the differentiation of OCs from bone marrow-derived 
      macrophages (BMMs) isolated from Trim21(-/-) and Ctsk-cre; Trim21(f/f) mice was 
      largely compromised compared to that of the littermate control mice. 
      Mechanistically, YAP1/beta-catenin signaling was identified and demonstrated to be 
      required for the Trim21-mediated osteogenic differentiation of BMSCs. More 
      importantly, the loss of Trim21 prevented ovariectomy (OVX)- and 
      lipopolysaccharide (LPS)-induced bone loss in vivo by orchestrating the coupling 
      of OBs and OCs through YAP1 signaling. Our current study demonstrated that Trim21 
      is crucial for regulating OB-mediated bone formation and OC-mediated bone 
      resorption, thereby providing a basis for exploring Trim21 as a novel 
      dual-targeting approach for treating osteoporosis and pathological bone loss.
CI  - (c) 2023. The Author(s).
FAU - Liu, Ri-Xu
AU  - Liu RX
AD  - Department of Bone and Joint Surgery, the First Affiliated Hospital of Jinan 
      University; Key Laboratory of Regenerative Medicine of Ministry of Education, 
      Jinan University, Guangzhou, 510630, Guangdong, China.
AD  - Department of Orthopedic and Spine Surgery, The First Affiliated Hospital of 
      Guangzhou Medical University, Guangzhou, 510120, Guangdong, China.
FAU - Gu, Rong-He
AU  - Gu RH
AD  - School of Basic Medical Sciences of Guangxi Medical University, the Fifth 
      Affiliated Hospital of Guangxi Medical University, Nanning, 530022, Guangxi, 
      China.
FAU - Li, Zhi-Peng
AU  - Li ZP
AD  - Department of Bone and Joint Surgery, the First Affiliated Hospital of Jinan 
      University; Key Laboratory of Regenerative Medicine of Ministry of Education, 
      Jinan University, Guangzhou, 510630, Guangdong, China.
FAU - Hao, Zhi-Quan
AU  - Hao ZQ
AD  - Department of Bone and Joint Surgery, the First Affiliated Hospital of Jinan 
      University; Key Laboratory of Regenerative Medicine of Ministry of Education, 
      Jinan University, Guangzhou, 510630, Guangdong, China.
FAU - Hu, Qin-Xiao
AU  - Hu QX
AD  - Department of Bone and Joint Surgery, the First Affiliated Hospital of Jinan 
      University; Key Laboratory of Regenerative Medicine of Ministry of Education, 
      Jinan University, Guangzhou, 510630, Guangdong, China.
FAU - Li, Zhen-Yan
AU  - Li ZY
AD  - Department of Bone and Joint Surgery, the First Affiliated Hospital of Jinan 
      University; Key Laboratory of Regenerative Medicine of Ministry of Education, 
      Jinan University, Guangzhou, 510630, Guangdong, China.
FAU - Wang, Xiao-Gang
AU  - Wang XG
AD  - Key Laboratory of Big Data-Based Precision Medicine, School of Engineering 
      Medicine, Beihang University, 100191, Beijing, China.
FAU - Tang, Wang
AU  - Tang W
AD  - Department of Bone and Joint Surgery, the First Affiliated Hospital of Jinan 
      University; Key Laboratory of Regenerative Medicine of Ministry of Education, 
      Jinan University, Guangzhou, 510630, Guangdong, China.
FAU - Wang, Xiao-He
AU  - Wang XH
AD  - Department of Bone and Joint Surgery, the First Affiliated Hospital of Jinan 
      University; Key Laboratory of Regenerative Medicine of Ministry of Education, 
      Jinan University, Guangzhou, 510630, Guangdong, China.
FAU - Zeng, Yu-Kai
AU  - Zeng YK
AD  - Department of Bone and Joint Surgery, the First Affiliated Hospital of Jinan 
      University; Key Laboratory of Regenerative Medicine of Ministry of Education, 
      Jinan University, Guangzhou, 510630, Guangdong, China.
FAU - Li, Zhen-Wei
AU  - Li ZW
AD  - Department of Bone and Joint Surgery, the First Affiliated Hospital of Jinan 
      University; Key Laboratory of Regenerative Medicine of Ministry of Education, 
      Jinan University, Guangzhou, 510630, Guangdong, China.
FAU - Dong, Qiu
AU  - Dong Q
AD  - Department of Bone and Joint Surgery, the First Affiliated Hospital of Jinan 
      University; Key Laboratory of Regenerative Medicine of Ministry of Education, 
      Jinan University, Guangzhou, 510630, Guangdong, China.
FAU - Zhu, Xiao-Feng
AU  - Zhu XF
AD  - Guangdong Provincial Key Laboratory of Traditional Chinese Medicine 
      Informatization, College of Pharmacy, Jinan University, Guangzhou, 510630, 
      Guangdong, China.
FAU - Chen, Di
AU  - Chen D
AUID- ORCID: 0000-0002-4258-3457
AD  - Research Center for Computer-aided Drug Discovery, Shenzhen Institute of Advanced 
      Technology, Chinese Academy of Sciences, 518005, Shenzhen, China.
FAU - Zhao, Ke-Wei
AU  - Zhao KW
AD  - Guangzhou Key Laboratory of Chinese Medicine Research on Prevention and Treatment 
      of Osteoporosis, the Third Affiliated Hospital of Guangzhou University of Chinese 
      Medicine, 510375, Guangzhou, China.
FAU - Zhang, Rong-Hua
AU  - Zhang RH
AD  - Guangdong Provincial Key Laboratory of Traditional Chinese Medicine 
      Informatization, College of Pharmacy, Jinan University, Guangzhou, 510630, 
      Guangdong, China. tzrh@jnu.edu.cn.
FAU - Zha, Zhen-Gang
AU  - Zha ZG
AD  - Department of Bone and Joint Surgery, the First Affiliated Hospital of Jinan 
      University; Key Laboratory of Regenerative Medicine of Ministry of Education, 
      Jinan University, Guangzhou, 510630, Guangdong, China. tbri@jnu.edu.cn.
FAU - Zhang, Huan-Tian
AU  - Zhang HT
AD  - Department of Bone and Joint Surgery, the First Affiliated Hospital of Jinan 
      University; Key Laboratory of Regenerative Medicine of Ministry of Education, 
      Jinan University, Guangzhou, 510630, Guangdong, China. zhanghuantian@jnu.edu.cn.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20231026
PL  - China
TA  - Bone Res
JT  - Bone research
JID - 101608652
RN  - 0 (beta Catenin)
RN  - 0 (SS-A antigen)
SB  - IM
MH  - Animals
MH  - Female
MH  - Humans
MH  - Mice
MH  - beta Catenin/genetics
MH  - Bone and Bones/metabolism
MH  - Cell Differentiation/genetics
MH  - *Osteogenesis/genetics
MH  - *Osteoporosis/genetics
PMC - PMC10603047
COIS- The authors declare no competing interests.
EDAT- 2023/10/27 00:42
MHDA- 2023/10/30 06:46
PMCR- 2023/10/26
CRDT- 2023/10/26 23:18
PHST- 2023/01/15 00:00 [received]
PHST- 2023/09/22 00:00 [accepted]
PHST- 2023/08/26 00:00 [revised]
PHST- 2023/10/30 06:46 [medline]
PHST- 2023/10/27 00:42 [pubmed]
PHST- 2023/10/26 23:18 [entrez]
PHST- 2023/10/26 00:00 [pmc-release]
AID - 10.1038/s41413-023-00296-3 [pii]
AID - 296 [pii]
AID - 10.1038/s41413-023-00296-3 [doi]
PST - epublish
SO  - Bone Res. 2023 Oct 26;11(1):56. doi: 10.1038/s41413-023-00296-3.