PMID- 36720704
OWN - NLM
STAT- MEDLINE
DCOM- 20230303
LR  - 20230303
IS  - 1757-7861 (Electronic)
IS  - 1757-7853 (Print)
IS  - 1757-7853 (Linking)
VI  - 15
IP  - 3
DP  - 2023 Mar
TI  - HUCMSC-derived Exosomes Suppress the Titanium Particles-induced Osteolysis in 
      Mice through Inhibiting CCL2 and CCL3.
PG  - 888-898
LID - 10.1111/os.13608 [doi]
AB  - OBJECTIVE: Wear particles induce inflammation and the further osteolysis around 
      the prosthesis, has been proven to be the main cause of aseptic hip joint 
      loosening. In this research, we aimed to clarify whether human umbilical cord 
      mesenchymal stem cells (HUCMSCs) could inhibit the titanium particles-induced 
      osteolysis and shed light upon its mechanism. METHODS: The expression of 
      chemokine (C-C motif) ligand 2 (CCL2), chemokine (C-C motif) ligand 3 (CCL3) and 
      chemokine (C-C motif) ligand 5 (CCL5) were examinjed in clinical specimens of 
      aseptic hip prosthesis loosening patients. Local injection of lentivirus that 
      knocked down CCL2 or CCL3 in a cranial osteolysis mice model were used to exam 
      the effect of CCL2 and CCL3 on titanium particles-induced osteolysis in vivo. 
      Transwell assay was used to examine the effect of CCL2 and CCL3 on titanium 
      particles-induced activation of macrophage in vitro. Furthermore, the therapeutic 
      effect of HUCMSCs, and exosomes from HUCMSCs were also examed in vivo and vitro. 
      Immunohistochemical and real-time PCR were used to examine the expression of 
      relative pathways. Analysis of variance (ANOVA) and Student-Newman-Keuls post hoc 
      t test were used to analyze the results and determine the statistical 
      significance of the differences. RESULTS: Results showed that titanium particles 
      caused the osteolysis at the mice cranial in vivo and a large number of 
      macrophages that migrated, while local injection of HUCMSCs and exosomes did 
      inhibit the cranial osteolysis and migration. An exosome inhibitor GW4869 
      significantly increased the osteolysis area in the mice cranium osteolysis model, 
      and increased the number of migrated macrophages. Immunohistochemical results 
      suggested that the expression of CCL2, CCL3 and CD68 in the cranial in Titanium 
      particles mice increased significantly, but was significantly reduced by HUCMSCs 
      or exosomes. HUCMSC and exosomes down-regulate the expression of CCL3 in vitro 
      and in vivo. CONCLUSION: HUCMSCs and HUCMSC-derived exosomes could suppress the 
      titanium particles-induced osteolysis in mice through inhibiting chemokine (C-C 
      motif) ligand 2, chemokine (C-C motif) ligand 3.
CI  - (c) 2023 The Authors. Orthopaedic Surgery published by Tianjin Hospital and John 
      Wiley & Sons Australia, Ltd.
FAU - Li, Shixun
AU  - Li S
AUID- ORCID: 0000-0003-3728-3537
AD  - Department of Orthopaedic Surgery, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen 
      University, Guangzhou, China.
FAU - Wu, Chuangran
AU  - Wu C
AD  - Department of Orthopaedic Surgery, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen 
      University, Guangzhou, China.
FAU - Lin, Sipeng
AU  - Lin S
AD  - Department of Orthopaedic Surgery, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen 
      University, Guangzhou, China.
FAU - Wen, Zhenkang
AU  - Wen Z
AD  - Department of Orthopaedic Surgery, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen 
      University, Guangzhou, China.
FAU - Luo, Wenqiang
AU  - Luo W
AD  - Department of Orthopaedic Surgery, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen 
      University, Guangzhou, China.
FAU - Li, Changchuan
AU  - Li C
AD  - Department of Orthopaedic Surgery, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen 
      University, Guangzhou, China.
FAU - Wang, Xiaoyan
AU  - Wang X
AD  - Guangzhou Saliai Stem Cell Science and Technology Co., LTD, Guangzhou, China.
FAU - Li, Xuejia
AU  - Li X
AD  - Guangzhou Saliai Stem Cell Science and Technology Co., LTD, Guangzhou, China.
FAU - Gao, Liangbin
AU  - Gao L
AUID- ORCID: 0000-0002-9333-7336
AD  - Department of Orthopaedic Surgery, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen 
      University, Guangzhou, China.
FAU - Ding, Yue
AU  - Ding Y
AUID- ORCID: 0000-0003-3562-1563
AD  - Department of Orthopaedic Surgery, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen 
      University, Guangzhou, China.
LA  - eng
GR  - 2021A1515110885/Guangdong Basic and Applied Basic Research Foundation/
GR  - 82072453/National Natural Science Foundation of China/
GR  - 202206010140/Science and Technology Program of Guangzhou/
PT  - Journal Article
DEP - 20230131
PL  - Australia
TA  - Orthop Surg
JT  - Orthopaedic surgery
JID - 101501666
RN  - 0 (Chemokine CCL2)
RN  - D1JT611TNE (Titanium)
RN  - 0 (Chemokine CCL3)
RN  - 0 (CCL2 protein, human)
RN  - 0 (Ccl3 protein, mouse)
SB  - IM
MH  - Humans
MH  - Animals
MH  - Mice
MH  - *Osteolysis
MH  - Chemokine CCL2/adverse effects/metabolism
MH  - Titanium
MH  - Chemokine CCL3
MH  - *Exosomes/metabolism
PMC - PMC9977603
OTO - NOTNLM
OT  - Aseptic loosening
OT  - CCL2
OT  - CCL3
OT  - Exosome
OT  - HUCMSC
OT  - Macrophage
EDAT- 2023/02/01 06:00
MHDA- 2023/03/04 06:00
PMCR- 2023/01/31
CRDT- 2023/01/31 22:23
PHST- 2022/10/28 00:00 [revised]
PHST- 2022/01/19 00:00 [received]
PHST- 2022/11/02 00:00 [accepted]
PHST- 2023/02/01 06:00 [pubmed]
PHST- 2023/03/04 06:00 [medline]
PHST- 2023/01/31 22:23 [entrez]
PHST- 2023/01/31 00:00 [pmc-release]
AID - OS13608 [pii]
AID - 10.1111/os.13608 [doi]
PST - ppublish
SO  - Orthop Surg. 2023 Mar;15(3):888-898. doi: 10.1111/os.13608. Epub 2023 Jan 31.