PMID- 36185580
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20221004
IS  - 2214-031X (Print)
IS  - 2214-0328 (Electronic)
IS  - 2214-031X (Linking)
VI  - 36
DP  - 2022 Sep
TI  - Triptolide attenuates inhibition of ankylosing spondylitis-derived mesenchymal 
      stem cells on the osteoclastogenesis through modulating exosomal transfer of 
      circ-0110634.
PG  - 132-144
LID - 10.1016/j.jot.2022.05.007 [doi]
AB  - BACKGROUND: Ankylosing spondylitis (AS) is featured by chronic inflammation of 
      the sacroiliac joints and spine as well as pathological new bone formation. 
      Osteoclastogenesis is a critical part in the development of bone formation. 
      Circular RNAs (circRNAs) are recent research hotspot in the RNA field while 
      rarely reported in osteoclastogenesis. METHODS: AS mesenchymal stem cells 
      (ASMSCs) and healthy donor mesenchymal stem cells (HDMSCs) were co-cultured with 
      peripheral blood mononuclear cells (PBMCs). RT-qPCR was applied to detect the 
      expression level of circ-0110634 in different exosomes. TRAP staining and TRAP 
      activity detection were performed to identify the effect of circ-0110634 
      overexpression on osteoclastogenesis. Bioinformatics analysis and mechanism 
      investigation were conducted to explore the downstream molecular mechanism of 
      circ-0110634. RESULTS: The effect of ASMSCs on PBMCs osteoclastogenesis is weaker 
      than that of HDMSCs. Circ-0110634 had higher expression in ASMSCs exosomes than 
      HDMSCs exosomes. Circ-0110634 overexpression suppressed the osteoclastogenesis. 
      Circ-0110634 bound to both TNF receptor associated factor 2 (TRAF2) and tumor 
      necrosis factor receptor II (TNFRII). Circ-0110634 also accelerated the 
      dimerization of TRAF2 to induce TRAF2 ubiquitination and degradation. 
      Circ-0110634 repressed the interplay between TRAF2 and TNFRII to inactivate the 
      nuclear factor-kappaB (NF-kappaB) and mitogen-activated protein kinases (MAPK) pathways. 
      Triptolide promoted the osteoclastogenesis of ASMSCs exosomes-treated PBMCs via 
      decreasing the exosomal transference of circ-0110634 in a dose-dependent manner. 
      Consistently, triptolide treatment stimulated osteoclastogenesis to alleviate the 
      arthritis of DBA/1 mice through suppressing circ-0110634. CONCLUSION: Our study 
      confirmed that triptolide targets circ-0110634 to ease the burden of AS patients. 
      THE TRANSLATIONAL POTENTIAL OF THIS ARTICLE: This study suggests triptolide 
      targets circ-0110634 to regulate osteoclastogenesis, which provides a novel 
      potential target in triptolide treatment for AS patients.
CI  - (c) 2022 The Authors.
FAU - Ji, Wei
AU  - Ji W
AD  - Department of Rheumatology, Affiliated Hospital of Nanjing University of Chinese 
      Medicine, Nanjing, 210023, Jiangsu, China.
FAU - Lu, Yueyang
AU  - Lu Y
AD  - School of Medicine and Holistic Integrative Medicine, Nanjing University of 
      Chinese Medicine, Nanjing, 210033, Jiangsu, China.
FAU - Ma, Zhuoyi
AU  - Ma Z
AD  - The Engineering Research Center of Synthetic Polypeptide Drug Discovery and 
      Evaluation, Jiangsu Province, China Pharmaceutical University, Nanjing, 210033, 
      Jiangsu, China.
FAU - Gan, Ke
AU  - Gan K
AD  - Department of Rheumatology, Affiliated Hospital of Nanjing University of Chinese 
      Medicine, Nanjing, 210023, Jiangsu, China.
FAU - Liu, Yan
AU  - Liu Y
AD  - Department of Rheumatology, Affiliated Hospital of Nanjing University of Chinese 
      Medicine, Nanjing, 210023, Jiangsu, China.
FAU - Cheng, Yue
AU  - Cheng Y
AD  - Department of Rheumatology, Affiliated Hospital of Nanjing University of Chinese 
      Medicine, Nanjing, 210023, Jiangsu, China.
FAU - Xu, Junliang
AU  - Xu J
AD  - Department of Rheumatology, Affiliated Hospital of Nanjing University of Chinese 
      Medicine, Nanjing, 210023, Jiangsu, China.
FAU - Liu, Shijia
AU  - Liu S
AD  - Department of Pharmacy, Affiliated Hospital of Nanjing University of Chinese 
      Medicine, Nanjing, 210023, Jiangsu, China.
FAU - Guo, Yunke
AU  - Guo Y
AD  - Department of Rheumatology, Affiliated Hospital of Nanjing University of Chinese 
      Medicine, Nanjing, 210023, Jiangsu, China.
FAU - Han, Shanhang
AU  - Han S
AD  - Department of Rheumatology, Affiliated Hospital of Nanjing University of Chinese 
      Medicine, Nanjing, 210023, Jiangsu, China.
FAU - Zhao, Zengyan
AU  - Zhao Z
AD  - Department of Rheumatology, Affiliated Hospital of Nanjing University of Chinese 
      Medicine, Nanjing, 210023, Jiangsu, China.
FAU - Xu, Hanmei
AU  - Xu H
AD  - China Pharmaceutical University, Nanjing, 210033, Jiangsu, China.
FAU - Qi, Weiyan
AU  - Qi W
AD  - The Engineering Research Center of Synthetic Polypeptide Drug Discovery and 
      Evaluation, Jiangsu Province, China Pharmaceutical University, Nanjing, 210033, 
      Jiangsu, China.
LA  - eng
PT  - Journal Article
DEP - 20220916
PL  - Singapore
TA  - J Orthop Translat
JT  - Journal of orthopaedic translation
JID - 101625127
PMC - PMC9489540
OTO - NOTNLM
OT  - Circ-0110634
OT  - Osteoclastogenesis
OT  - TRAF2
OT  - Triptolide
OT  - Ubiquitination
COIS- The authors have no conflicts of interest relevant to this article.
EDAT- 2022/10/04 06:00
MHDA- 2022/10/04 06:01
PMCR- 2022/09/16
CRDT- 2022/10/03 04:21
PHST- 2021/08/03 00:00 [received]
PHST- 2022/03/30 00:00 [revised]
PHST- 2022/05/19 00:00 [accepted]
PHST- 2022/10/03 04:21 [entrez]
PHST- 2022/10/04 06:00 [pubmed]
PHST- 2022/10/04 06:01 [medline]
PHST- 2022/09/16 00:00 [pmc-release]
AID - S2214-031X(22)00044-4 [pii]
AID - 10.1016/j.jot.2022.05.007 [doi]
PST - epublish
SO  - J Orthop Translat. 2022 Sep 16;36:132-144. doi: 10.1016/j.jot.2022.05.007. 
      eCollection 2022 Sep.