PMID- 37976598
OWN - NLM
STAT- MEDLINE
DCOM- 20231121
LR  - 20231121
IS  - 1878-1705 (Electronic)
IS  - 1567-5769 (Linking)
VI  - 125
IP  - Pt B
DP  - 2023 Dec
TI  - Diabetic and nondiabetic BMSC-derived exosomes affect bone regeneration via 
      regulating miR-17-5p/SMAD7 axis.
PG  - 111190
LID - S1567-5769(23)01517-5 [pii]
LID - 10.1016/j.intimp.2023.111190 [doi]
AB  - Diabetic bone disease (DBD) is a complication of diabetes mellitus (DM) and is 
      characterized by impaired osteocyte function and delayed bone remodeling due to 
      high blood glucose levels and sustained release of inflammatory factors. Recent 
      studies show that the regulation of osteoblasts (OBs) by bone marrow stromal 
      cells (BMSCs) is an important mechanism in alleviating DBD and that exosomes are 
      recognized as the key medium. Mesenchymal stem cell-derived exosome (MSC-Exos) 
      therapy is a promising approach to facilitate tissue repair. However, the 
      influence of exosomes from diabetic conditioned BMSCs on OBs and bone 
      regeneration, as well as the underlying mechanism, are still elusive. Here, we 
      used high-glucose medium to mimic diabetic conditions and normal-glucose medium 
      as control to mimic nondiabetic conditions in vitro and found that microRNA-17 
      (miR-17) was downregulated in diabetic-conditioned BMSC-derived exosomes 
      (HG-Exos), HG-Exo-co-cultured osteoblasts, and the skull of rats with type 2 
      diabetes mellitus (T2DM). Further experiment concluded that nondiabetic 
      conditioned BMSC-Exos (NG-Exos) promoted the osteogenesis of OBs and bone 
      regeneration of rats with T2DM via upregulation of miR-17. Compare with NG-Exos, 
      HG-Exos impeded osteogenesis of OBs in vitro and bone regeneration of rats in 
      vivo by downregulation of miR-17. Moreover, miR-17 promoted bone regeneration by 
      targeting SMAD7, which was further proved to have a negative effect on 
      osteogenesis. Taken together, nondiabetic BMSC-derived exosomes greatly foster 
      bone regeneration, whereas diabetic BMSC-derived exosomes undermine the promotion 
      effect of MSC-Exos by regulating the miR-17/SMAD7 axis. These findings provide 
      support for the miR-17-5p/SMAD7 axis as a promising therapeutic target to treat 
      DBD.
CI  - Copyright (c) 2023 Elsevier B.V. All rights reserved.
FAU - Li, Zechuan
AU  - Li Z
AD  - Department of Implantology, School and Hospital of Stomatology, Cheeloo College 
      of Medicine, Shandong University & Shandong Key Laboratory of Oral Tissue 
      Regeneration & Shandong Engineering Research Center of Dental Materials and Oral 
      Tissue Regeneration & Shandong Provincial Clinical Research Center for Oral 
      Diseases, No. 44-1 Wenhua Road West, 250012 Jinan, Shandong, China.
FAU - Zhang, Bing
AU  - Zhang B
AD  - Department of Health Care, School and Hospital of Stomatology, Cheeloo College of 
      Medicine, Shandong University & Shandong Key Laboratory of Oral Tissue 
      Regeneration & Shandong Engineering Research Center of Dental Materials and Oral 
      Tissue Regeneration & Shandong Provincial Clinical Research Center for Oral 
      Diseases, No. 44-1 Wenhua Road West, 250012 Jinan, Shandong, China.
FAU - Shang, Jiaming
AU  - Shang J
AD  - Department of Prosthodontics, School and Hospital of Stomatology, Cheeloo College 
      of Medicine, Shandong University & Shandong Key Laboratory of Oral Tissue 
      Regeneration & Shandong Engineering Research Center of Dental Materials and Oral 
      Tissue Regeneration & Shandong Provincial Clinical Research Center for Oral 
      Diseases, No. 44-1 Wenhua Road West, 250012 Jinan, Shandong, China.
FAU - Wang, Yanan
AU  - Wang Y
AD  - Department of Implantology, School and Hospital of Stomatology, Cheeloo College 
      of Medicine, Shandong University & Shandong Key Laboratory of Oral Tissue 
      Regeneration & Shandong Engineering Research Center of Dental Materials and Oral 
      Tissue Regeneration & Shandong Provincial Clinical Research Center for Oral 
      Diseases, No. 44-1 Wenhua Road West, 250012 Jinan, Shandong, China.
FAU - Jia, Linglu
AU  - Jia L
AD  - Department of Prosthodontics, School and Hospital of Stomatology, Cheeloo College 
      of Medicine, Shandong University & Shandong Key Laboratory of Oral Tissue 
      Regeneration & Shandong Engineering Research Center of Dental Materials and Oral 
      Tissue Regeneration & Shandong Provincial Clinical Research Center for Oral 
      Diseases, No. 44-1 Wenhua Road West, 250012 Jinan, Shandong, China.
FAU - She, Xiao
AU  - She X
AD  - Department of Implantology, School and Hospital of Stomatology, Cheeloo College 
      of Medicine, Shandong University & Shandong Key Laboratory of Oral Tissue 
      Regeneration & Shandong Engineering Research Center of Dental Materials and Oral 
      Tissue Regeneration & Shandong Provincial Clinical Research Center for Oral 
      Diseases, No. 44-1 Wenhua Road West, 250012 Jinan, Shandong, China.
FAU - Xu, Xin
AU  - Xu X
AD  - Department of Implantology, School and Hospital of Stomatology, Cheeloo College 
      of Medicine, Shandong University & Shandong Key Laboratory of Oral Tissue 
      Regeneration & Shandong Engineering Research Center of Dental Materials and Oral 
      Tissue Regeneration & Shandong Provincial Clinical Research Center for Oral 
      Diseases, No. 44-1 Wenhua Road West, 250012 Jinan, Shandong, China.
FAU - Zhang, Dongjiao
AU  - Zhang D
AD  - Department of Implantology, School and Hospital of Stomatology, Cheeloo College 
      of Medicine, Shandong University & Shandong Key Laboratory of Oral Tissue 
      Regeneration & Shandong Engineering Research Center of Dental Materials and Oral 
      Tissue Regeneration & Shandong Provincial Clinical Research Center for Oral 
      Diseases, No. 44-1 Wenhua Road West, 250012 Jinan, Shandong, China.
FAU - Guo, Jing
AU  - Guo J
AD  - Engineering Laboratory for Biomaterials and Tissue Regeneration, Ningbo 
      Stomatology Hospital, No. 435 Xinxing Road, Ningbo 315042, Zhejiang, China; 
      Savaid Stomatology School of Hangzhou Medical College, No. 1 Pinghai Road, 
      Hangzhou 310051, Zhejiang, China.
FAU - Zhang, Fan
AU  - Zhang F
AD  - Department of Orthodontics, School and Hospital of Stomatology, Cheeloo College 
      of Medicine, Shandong University & Shandong Key Laboratory of Oral Tissue 
      Regeneration & Shandong Engineering Research Center of Dental Materials and Oral 
      Tissue Regeneration & Shandong Provincial Clinical Research Center for Oral 
      Diseases, No. 44-1 Wenhua Road West, 250012 Jinan, Shandong, China. Electronic 
      address: zhfan@sdu.edu.cn.
LA  - eng
PT  - Journal Article
DEP - 20231115
PL  - Netherlands
TA  - Int Immunopharmacol
JT  - International immunopharmacology
JID - 100965259
RN  - IY9XDZ35W2 (Glucose)
RN  - 0 (MicroRNAs)
RN  - 0 (MIRN17 microRNA, rat)
SB  - IM
MH  - Animals
MH  - Rats
MH  - *Diabetes Mellitus, Type 2
MH  - *Exosomes
MH  - Bone Regeneration/genetics
MH  - Glucose
MH  - *MicroRNAs/genetics
OTO - NOTNLM
OT  - Diabetes mellitus
OT  - Diabetic bone disease
OT  - Exosomes
OT  - Osteogenesis
OT  - SMAD7
OT  - microRNA
COIS- Declaration of Competing Interest The authors declare that they have no known 
      competing financial interests or personal relationships that could have appeared 
      to influence the work reported in this paper.
EDAT- 2023/11/18 11:42
MHDA- 2023/11/21 06:41
CRDT- 2023/11/17 18:01
PHST- 2023/07/29 00:00 [received]
PHST- 2023/11/03 00:00 [revised]
PHST- 2023/11/03 00:00 [accepted]
PHST- 2023/11/21 06:41 [medline]
PHST- 2023/11/18 11:42 [pubmed]
PHST- 2023/11/17 18:01 [entrez]
AID - S1567-5769(23)01517-5 [pii]
AID - 10.1016/j.intimp.2023.111190 [doi]
PST - ppublish
SO  - Int Immunopharmacol. 2023 Dec;125(Pt B):111190. doi: 
      10.1016/j.intimp.2023.111190. Epub 2023 Nov 15.