PMID- 38491721
OWN - NLM
STAT- Publisher
LR  - 20240316
IS  - 1544-0591 (Electronic)
IS  - 0022-0345 (Linking)
DP  - 2024 Mar 15
TI  - AZGP1 Aggravates Macrophage M1 Polarization and Pyroptosis in Periodontitis.
PG  - 220345241235616
LID - 10.1177/00220345241235616 [doi]
AB  - Periodontal tissue destruction in periodontitis is a consequence of the host 
      inflammatory response to periodontal pathogens, which could be aggravated in the 
      presence of type 2 diabetes mellitus (T2DM). Accumulating evidence highlights the 
      intricate involvement of macrophage-mediated inflammation in the pathogenesis of 
      periodontitis under both normal and T2DM conditions. However, the underlying 
      mechanism remains elusive. Alpha-2-glycoprotein 1 (AZGP1), a glycoprotein 
      featuring an MHC-I domain, has been implicated in both inflammation and metabolic 
      disorders. In this study, we found that AZGP1 was primarily colocalized with 
      macrophages in periodontitis tissues. AZGP1 was increased in periodontitis 
      compared with controls, which was further elevated when accompanied by T2DM. 
      Adeno-associated virus-mediated overexpression of Azgp1 in the periodontium 
      significantly enhanced periodontal inflammation and alveolar bone loss, 
      accompanied by elevated M1 macrophages and pyroptosis in murine models of 
      periodontitis and T2DM-associated periodontitis, while Azgp1(-/-) mice exhibited 
      opposite effects. In primary bone marrow-derived macrophages stimulated by 
      lipopolysaccharide (LPS) or LPS and palmitic acid (PA), overexpression or 
      knockout of Azgp1 markedly upregulated or suppressed, respectively, the 
      expression of macrophage M1 markers and key components of the NLR Family Pyrin 
      Domain Containing 3 (NLRP3)/caspase-1 signaling. Moreover, conditioned medium 
      from Azgp1-overexpressed macrophages under LPS or LPS+PA stimulation induced 
      higher inflammatory activation and lower osteogenic differentiation in human 
      periodontal ligament stem cells (hPDLSCs). Furthermore, elevated M1 polarization 
      and pyroptosis in macrophages and associated detrimental effects on hPDLSCs 
      induced by Azgp1 overexpression could be rescued by NLRP3 or caspase-1 
      inhibition. Collectively, our study elucidated that AZGP1 could aggravate 
      periodontitis by promoting macrophage M1 polarization and pyroptosis through the 
      NLRP3/casapse-1 pathway, which was accentuated in T2DM-associated periodontitis. 
      This finding deepens the understanding of AZGP1 in the pathogenesis of 
      periodontitis and suggests AZGP1 as a crucial link mediating the adverse effects 
      of diabetes on periodontal inflammation.
FAU - Yang, S
AU  - Yang S
AD  - College of Stomatology, Chongqing Medical University, Chongqing, China.
AD  - Chongqing Key Laboratory of Oral Diseases and Biomedical Sciences, Chongqing, 
      China.
AD  - Chongqing Municipal Key Laboratory of Oral Biomedical Engineering of Higher 
      Education, Chongqing, China.
FAU - Yin, Y
AU  - Yin Y
AD  - College of Stomatology, Chongqing Medical University, Chongqing, China.
AD  - Chongqing Key Laboratory of Oral Diseases and Biomedical Sciences, Chongqing, 
      China.
AD  - Chongqing Municipal Key Laboratory of Oral Biomedical Engineering of Higher 
      Education, Chongqing, China.
FAU - Sun, Y
AU  - Sun Y
AD  - College of Stomatology, Chongqing Medical University, Chongqing, China.
AD  - Chongqing Key Laboratory of Oral Diseases and Biomedical Sciences, Chongqing, 
      China.
AD  - Chongqing Municipal Key Laboratory of Oral Biomedical Engineering of Higher 
      Education, Chongqing, China.
FAU - Ai, D
AU  - Ai D
AD  - College of Stomatology, Chongqing Medical University, Chongqing, China.
AD  - Chongqing Key Laboratory of Oral Diseases and Biomedical Sciences, Chongqing, 
      China.
AD  - Chongqing Municipal Key Laboratory of Oral Biomedical Engineering of Higher 
      Education, Chongqing, China.
FAU - Xia, X
AU  - Xia X
AD  - Department of Endocrinology, The Second Affiliated Hospital, Chongqing Medical 
      University, Chongqing, China.
FAU - Xu, X
AU  - Xu X
AD  - College of Stomatology, Chongqing Medical University, Chongqing, China.
AD  - Chongqing Key Laboratory of Oral Diseases and Biomedical Sciences, Chongqing, 
      China.
AD  - Chongqing Municipal Key Laboratory of Oral Biomedical Engineering of Higher 
      Education, Chongqing, China.
FAU - Song, J
AU  - Song J
AD  - College of Stomatology, Chongqing Medical University, Chongqing, China.
AD  - Chongqing Key Laboratory of Oral Diseases and Biomedical Sciences, Chongqing, 
      China.
AD  - Chongqing Municipal Key Laboratory of Oral Biomedical Engineering of Higher 
      Education, Chongqing, China.
LA  - eng
PT  - Journal Article
DEP - 20240315
PL  - United States
TA  - J Dent Res
JT  - Journal of dental research
JID - 0354343
SB  - IM
OTO - NOTNLM
OT  - bone loss
OT  - inflammation
OT  - innate immunity
OT  - periodontal diseases
OT  - regulated cell death
OT  - type 2 diabetes
COIS- Declaration of Conflicting InterestsThe authors declared no potential conflicts 
      of interest with respect to the research, authorship, and/or publication of this 
      article.
EDAT- 2024/03/16 21:44
MHDA- 2024/03/16 21:44
CRDT- 2024/03/16 01:12
PHST- 2024/03/16 21:44 [medline]
PHST- 2024/03/16 21:44 [pubmed]
PHST- 2024/03/16 01:12 [entrez]
AID - 10.1177/00220345241235616 [doi]
PST - aheadofprint
SO  - J Dent Res. 2024 Mar 15:220345241235616. doi: 10.1177/00220345241235616.