PMID- 35050801
OWN - NLM
STAT- MEDLINE
DCOM- 20220523
LR  - 20220614
IS  - 1544-0591 (Electronic)
IS  - 0022-0345 (Linking)
VI  - 101
IP  - 6
DP  - 2022 Jun
TI  - Leptin Aggravates Periodontitis by Promoting M1 Polarization via NLRP3.
PG  - 675-685
LID - 10.1177/00220345211059418 [doi]
AB  - Periodontitis is characterized by periodontal pocket formation, loss of 
      attachment, and alveolar bone resorption. Both innate and adaptive immunity are 
      involved in the pathogenesis of this oral chronic inflammatory disease. 
      Accumulating evidence indicates a critical role of leptin in periodontal 
      diseases. However, the mechanism by which leptin promotes periodontitis 
      pathogenesis remains unclear. In the present study, we observed an elevated 
      expression of leptin in the serum of periodontitis mice compared to that in 
      healthy controls. There was a higher extent of M1 phenotype macrophage 
      infiltration in mice periodontitis samples than in healthy controls. A positive 
      correlation was observed between the serum leptin levels and M1 macrophages. 
      Treatment with leptin increased M1 macrophage polarization and decreased M2 
      macrophage polarization in RAW 264.7 cells. Moreover, leptin facilitated 
      lipopolysaccharide (LPS)-induced M1 phenotype macrophage polarization in RAW 
      264.7 cells. In bone marrow-derived macrophages (BMDMs) generated from 
      leptin-deficient obese (ob/ob) mice, M1 macrophage polarization was significantly 
      attenuated after LPS stimulation compared to the healthy controls. With regards 
      to the molecular mechanism, we found that leptin activated the NOD-like receptor 
      family pyrin domain containing 3 (NLRP3) inflammasome and promoted M1 
      polarization via the NLRP3 inflammasome in vitro. In BMDMs generated from 
      Nlrp3(-/-) mice, M1 macrophage polarization was significantly attenuated after 
      synchronous stimulation with leptin and LPS compared with BMDMs produced by 
      healthy controls. The NLRP3 inhibitor MCC950 also prevented leptin-mediated M1 
      macrophage polarization in RAW 264.7 cells. Nlrp3(-/-) periodontitis models 
      indicated that leptin aggravates the periodontal response to the ligature by 
      promoting M1 macrophage polarization via the NLRP3 inflammasome. Taken together, 
      we show that leptin promotes the progression of periodontitis via proinflammatory 
      M1 macrophage skewing, and targeting leptin/NLRP3 signaling may be a feasible 
      approach for treating periodontitis.
FAU - Han, Y
AU  - Han Y
AD  - Department of Orthodontics, Peking University School and Hospital of Stomatology, 
      Beijing, China.
AD  - National Center of Stomatology, National Clinical Research Center for Oral 
      Diseases, National Engineering Laboratory for Digital and Material Technology of 
      Stomatology, Beijing, China.
FAU - Huang, Y
AU  - Huang Y
AD  - Department of Orthodontics, Peking University School and Hospital of Stomatology, 
      Beijing, China.
AD  - National Center of Stomatology, National Clinical Research Center for Oral 
      Diseases, National Engineering Laboratory for Digital and Material Technology of 
      Stomatology, Beijing, China.
FAU - Gao, P
AU  - Gao P
AD  - Key Laboratory of Cell Proliferation and Differentiation of the Ministry of 
      Education, School of Life Sciences, Peking University, Beijing, China 
      Peking-Tsinghua Center for Life Sciences, Beijing, China.
FAU - Yang, Q
AU  - Yang Q
AD  - Department of Orthodontics, Peking University School and Hospital of Stomatology, 
      Beijing, China.
AD  - National Center of Stomatology, National Clinical Research Center for Oral 
      Diseases, National Engineering Laboratory for Digital and Material Technology of 
      Stomatology, Beijing, China.
FAU - Jia, L
AU  - Jia L
AD  - National Center of Stomatology, National Clinical Research Center for Oral 
      Diseases, National Engineering Laboratory for Digital and Material Technology of 
      Stomatology, Beijing, China.
AD  - Department of Oral and Maxillofacial Surgery, Peking University School and 
      Hospital of Stomatology, Beijing, China.
AD  - Central Laboratory, Peking University School and Hospital of Stomatology, 
      Beijing, China.
FAU - Zheng, Y
AU  - Zheng Y
AD  - Department of Orthodontics, Peking University School and Hospital of Stomatology, 
      Beijing, China.
AD  - National Center of Stomatology, National Clinical Research Center for Oral 
      Diseases, National Engineering Laboratory for Digital and Material Technology of 
      Stomatology, Beijing, China.
FAU - Li, W
AU  - Li W
AD  - Department of Orthodontics, Peking University School and Hospital of Stomatology, 
      Beijing, China.
AD  - National Center of Stomatology, National Clinical Research Center for Oral 
      Diseases, National Engineering Laboratory for Digital and Material Technology of 
      Stomatology, Beijing, China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20220120
PL  - United States
TA  - J Dent Res
JT  - Journal of dental research
JID - 0354343
RN  - 0 (Inflammasomes)
RN  - 0 (Leptin)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (NLR Family, Pyrin Domain-Containing 3 Protein)
RN  - 0 (Nlrp3 protein, mouse)
SB  - IM
MH  - *Alveolar Bone Loss/prevention & control
MH  - Animals
MH  - Inflammasomes
MH  - *Leptin
MH  - Lipopolysaccharides/pharmacology
MH  - *Macrophage Activation
MH  - Mice
MH  - *NLR Family, Pyrin Domain-Containing 3 Protein/genetics/metabolism
MH  - *Periodontitis/pathology
OTO - NOTNLM
OT  - NLRP3 inflammasome
OT  - alveolar bone loss
OT  - inflammation
OT  - innate immunity
OT  - macrophage polarization
OT  - periodontal diseases
EDAT- 2022/01/21 06:00
MHDA- 2022/05/24 06:00
CRDT- 2022/01/20 17:38
PHST- 2022/01/21 06:00 [pubmed]
PHST- 2022/05/24 06:00 [medline]
PHST- 2022/01/20 17:38 [entrez]
AID - 10.1177/00220345211059418 [doi]
PST - ppublish
SO  - J Dent Res. 2022 Jun;101(6):675-685. doi: 10.1177/00220345211059418. Epub 2022 
      Jan 20.