PMID- 32858254
OWN - NLM
STAT- MEDLINE
DCOM- 20210617
LR  - 20210617
IS  - 1873-2763 (Electronic)
IS  - 1873-2763 (Linking)
VI  - 143
DP  - 2021 Feb
TI  - Abnormal macrophage polarization impedes the healing of diabetes-associated tooth 
      sockets.
PG  - 115618
LID - S8756-3282(20)30398-7 [pii]
LID - 10.1016/j.bone.2020.115618 [doi]
AB  - Patients with poorly controlled type 2 diabetes mellitus (T2DM) often experience 
      delayed tooth extraction socket (TES) healing. Delayed healing is often 
      associated with an aberrant inflammatory response orchestrated by either M1 
      pro-inflammatory or M2 anti-inflammatory macrophages. However, the precise 
      mechanism for the attenuated TES healing remains unclear. Here we used 
      diet-induced T2DM mice as a model to study TES. Compared with the control group, 
      the T2DM group showed delayed TES healing and diminished expression of osteogenic 
      and angiogenic genetic profiles. Meanwhile, we detected a more inflammatory 
      profile, with more M1 macrophages and TNF-alpha expression and less M2 macrophages 
      and PPARgamma expression, in TES in the T2DM group when compared to control mice. In 
      vitro co-culture models showed that M1 macrophages inhibited the osteogenic 
      capacity of bone marrow stromal cells and the angiogenic capacity of endothelial 
      cells while M2 macrophages showed an opposite effect. In addition, we constructed 
      a gelatin/beta-TCP scaffold with IL-4 to induce macrophage transformation towards M2 
      polarization. In vitro analyses of the hybrid scaffold revealed sustained release 
      of IL-4 and a phenotype switch to M2 macrophages. Finally, we demonstrated that 
      sustained IL-4 release significantly increased expression of osteogenic and 
      angiogenic genetic profiles and improved TES healing in T2DM mice. Together, we 
      report that increased M1 and decreased M2 macrophage polarization may be 
      responsible for delayed TES healing in T2DM patients through abnormal expression 
      of TNF-alpha and PPARgamma. This imbalance negatively influences osteogenesis and 
      angiogenesis, two of the most important biological factors in bone wound healing. 
      Enhancing M2 macrophage polarization with IL-4 delivery system may represent a 
      potential strategy for promoting the healing of TES in T2DM patients.
CI  - Copyright (c) 2020 Elsevier Inc. All rights reserved.
FAU - Shen, Xiang
AU  - Shen X
AD  - Jiangsu Key Laboratory of Oral Diseases, Nanjing Medical University, China; 
      Department of Stomatology, Affiliated Hospital of Nantong University, China.
FAU - Shen, Xin
AU  - Shen X
AD  - Jiangsu Key Laboratory of Oral Diseases, Nanjing Medical University, China; 
      Department of Oral and Maxillofacial Surgery, Affiliated Hospital of Stomatology, 
      Nanjing Medical University, China.
FAU - Li, Bang
AU  - Li B
AD  - Jiangsu Key Laboratory of Oral Diseases, Nanjing Medical University, China; 
      Department of Oral and Maxillofacial Surgery, Affiliated Hospital of Stomatology, 
      Nanjing Medical University, China.
FAU - Zhu, Weiwen
AU  - Zhu W
AD  - Jiangsu Key Laboratory of Oral Diseases, Nanjing Medical University, China; 
      Department of Oral and Maxillofacial Surgery, Affiliated Hospital of Stomatology, 
      Nanjing Medical University, China.
FAU - Fu, Yu
AU  - Fu Y
AD  - Jiangsu Key Laboratory of Oral Diseases, Nanjing Medical University, China; 
      Department of Oral and Maxillofacial Surgery, Affiliated Hospital of Stomatology, 
      Nanjing Medical University, China.
FAU - Xu, Rongyao
AU  - Xu R
AD  - Jiangsu Key Laboratory of Oral Diseases, Nanjing Medical University, China; 
      Department of Oral and Maxillofacial Surgery, Affiliated Hospital of Stomatology, 
      Nanjing Medical University, China.
FAU - Du, Yifei
AU  - Du Y
AD  - Jiangsu Key Laboratory of Oral Diseases, Nanjing Medical University, China; 
      Department of Oral and Maxillofacial Surgery, Affiliated Hospital of Stomatology, 
      Nanjing Medical University, China.
FAU - Cheng, Jie
AU  - Cheng J
AD  - Jiangsu Key Laboratory of Oral Diseases, Nanjing Medical University, China; 
      Department of Oral and Maxillofacial Surgery, Affiliated Hospital of Stomatology, 
      Nanjing Medical University, China.
FAU - Jiang, Hongbing
AU  - Jiang H
AD  - Jiangsu Key Laboratory of Oral Diseases, Nanjing Medical University, China; 
      Department of Oral and Maxillofacial Surgery, Affiliated Hospital of Stomatology, 
      Nanjing Medical University, China. Electronic address: jhb@njmu.edu.cn.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20200826
PL  - United States
TA  - Bone
JT  - Bone
JID - 8504048
SB  - IM
MH  - Animals
MH  - *Diabetes Mellitus, Type 2
MH  - Endothelial Cells
MH  - Humans
MH  - Macrophages
MH  - Mice
MH  - *Tooth Socket
MH  - Wound Healing
OTO - NOTNLM
OT  - Bone wound healing
OT  - Gelatin/beta-TCP scaffold
OT  - IL-4
OT  - Inflammation
OT  - Macrophage polarization
OT  - Tooth extraction socket
OT  - Type 2 diabetes mellitus
EDAT- 2020/08/29 06:00
MHDA- 2021/06/22 06:00
CRDT- 2020/08/29 06:00
PHST- 2020/06/03 00:00 [received]
PHST- 2020/08/23 00:00 [revised]
PHST- 2020/08/24 00:00 [accepted]
PHST- 2020/08/29 06:00 [pubmed]
PHST- 2021/06/22 06:00 [medline]
PHST- 2020/08/29 06:00 [entrez]
AID - S8756-3282(20)30398-7 [pii]
AID - 10.1016/j.bone.2020.115618 [doi]
PST - ppublish
SO  - Bone. 2021 Feb;143:115618. doi: 10.1016/j.bone.2020.115618. Epub 2020 Aug 26.