PMID- 35151924
OWN - NLM
STAT- MEDLINE
DCOM- 20220422
LR  - 20220531
IS  - 1878-7568 (Electronic)
IS  - 1742-7061 (Linking)
VI  - 142
DP  - 2022 Apr 1
TI  - LncRNA Neat1 promotes the macrophage inflammatory response and acts as a 
      therapeutic target in titanium particle-induced osteolysis.
PG  - 345-360
LID - S1742-7061(22)00084-8 [pii]
LID - 10.1016/j.actbio.2022.02.007 [doi]
AB  - Aseptic loosening (AL), secondary to particle-caused periprosthetic osteolysis, 
      is one of the main reasons of artificial joint failure. Suppressing the 
      macrophage inflammatory response caused by wear particles extends the life of 
      prosthesis, and the long noncoding RNAs (lncRNAs) may play a predominant part in 
      it. Here, titanium particles' (TiPs') stimulation increases both the cytoplasmic 
      and nuclear levels of lncRNA Neat1 in bone marrow derived macrophages (BMDMs), 
      which further induces the inflammatory response. Mechanically, Neat1 facilitates 
      Bruton's tyrosine kinase (BTK) transcription by reducing the transcriptional 
      factor KLF4, which further activates the NF-kappaB pathway, NLRP3 inflammation, and 
      M1 polarization in BMDMs. Cytoplasmic Neat1 also works as an miRNA sponge in 
      miR-188-5p-regulated BTK expression in the post-transcriptional stage. In vivo, 
      Neat1 downregulation can reduce the TiP-induced pro-inflammatory factors and 
      reverse the osteolysis induced by BTK overexpression. In addition, the PLGA-based 
      microparticles loaded with si-Neat1 are developed for the treatment of the mouse 
      calvarial osteolysis model via local injection, presenting satisfactory 
      anti-osteolysis efficacy. These findings indicate that Neat1 is a key regulator 
      of AL. STATEMENT OF SIGNIFICANCE: Due to released particles, aseptic loosening 
      (AL) is the most common reason for prosthesis failure and surgical revision and 
      represents a substantial economic burden worldwide. Herein, we reported that 
      lncRNA Neat1 is a key regulator in regulating wear particles-induced osteolysis 
      by activating NF-kappaB pathway, NLRP3 inflammation and M1 polarization via BTK, and 
      the underlying mechanisms of Neat1-BTK interaction were further portrayed. For 
      potential clinical application, the microparticles are developed for effective 
      si-Neat1 delivery, leading to a dramatically enhanced effect for the treatment of 
      osteolysis, which might be a novel strategy to extend the life of the implant.
CI  - Copyright (c) 2022. Published by Elsevier Ltd.
FAU - Lin, Sipeng
AU  - Lin S
AD  - Department of Orthopedic Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen 
      University, Guangzhou, 510000, China.
FAU - Wen, Zhenkang
AU  - Wen Z
AD  - Department of Orthopedic Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen 
      University, Guangzhou, 510000, China.
FAU - Li, Shixun
AU  - Li S
AD  - Department of Orthopedic Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen 
      University, Guangzhou, 510000, China.
FAU - Chen, Zhong
AU  - Chen Z
AD  - Department of Orthopedic Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen 
      University, Guangzhou, 510000, China.
FAU - Li, Changchuan
AU  - Li C
AD  - Department of Orthopedic Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen 
      University, Guangzhou, 510000, China.
FAU - Ouyang, Zhuji
AU  - Ouyang Z
AD  - Department of Orthopedic Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen 
      University, Guangzhou, 510000, China.
FAU - Lin, Chuangxin
AU  - Lin C
AD  - Department of Orthopedic Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen 
      University, Guangzhou, 510000, China.
FAU - Kuang, Manyuan
AU  - Kuang M
AD  - Department of Orthopedic Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen 
      University, Guangzhou, 510000, China.
FAU - Xue, Chunyu
AU  - Xue C
AD  - Department of Orthopedic Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen 
      University, Guangzhou, 510000, China.
FAU - Ding, Yue
AU  - Ding Y
AD  - Department of Orthopedic Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen 
      University, Guangzhou, 510000, China. Electronic address: 
      dingyue@mail.sysu.edu.cn.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20220210
PL  - England
TA  - Acta Biomater
JT  - Acta biomaterialia
JID - 101233144
RN  - 0 (NEAT1 long non-coding RNA, mouse)
RN  - 0 (NF-kappa B)
RN  - 0 (NLR Family, Pyrin Domain-Containing 3 Protein)
RN  - 0 (RNA, Long Noncoding)
RN  - D1JT611TNE (Titanium)
SB  - IM
MH  - Animals
MH  - Inflammation/metabolism
MH  - *Joint Prosthesis/adverse effects
MH  - Macrophages/metabolism
MH  - Mice
MH  - NF-kappa B/metabolism
MH  - NLR Family, Pyrin Domain-Containing 3 Protein
MH  - *Osteolysis/chemically induced/drug therapy
MH  - *RNA, Long Noncoding/genetics/metabolism
MH  - Titanium/adverse effects
OTO - NOTNLM
OT  - Aseptic loosening
OT  - Macrophage inflammatory response
OT  - Microparticles
OT  - Osteolysis
OT  - lncRNAs
COIS- Declaration of Competing Interest The authors declare no competing interests.
EDAT- 2022/02/14 06:00
MHDA- 2022/04/23 06:00
CRDT- 2022/02/13 20:29
PHST- 2021/10/09 00:00 [received]
PHST- 2022/01/18 00:00 [revised]
PHST- 2022/02/07 00:00 [accepted]
PHST- 2022/02/14 06:00 [pubmed]
PHST- 2022/04/23 06:00 [medline]
PHST- 2022/02/13 20:29 [entrez]
AID - S1742-7061(22)00084-8 [pii]
AID - 10.1016/j.actbio.2022.02.007 [doi]
PST - ppublish
SO  - Acta Biomater. 2022 Apr 1;142:345-360. doi: 10.1016/j.actbio.2022.02.007. Epub 
      2022 Feb 10.