PMID- 35639178
OWN - NLM
STAT- MEDLINE
DCOM- 20220602
LR  - 20220830
IS  - 1420-9071 (Electronic)
IS  - 1420-682X (Print)
IS  - 1420-682X (Linking)
VI  - 79
IP  - 6
DP  - 2022 May 31
TI  - Trigeminal neurons control immune-bone cell interaction and metabolism in apical 
      periodontitis.
PG  - 330
LID - 10.1007/s00018-022-04335-w [doi]
LID - 330
AB  - Apical periodontitis (AP) is an inflammatory disease occurring following tooth 
      infection with distinct osteolytic activity. Despite increasing evidence that 
      sensory neurons participate in regulation of non-neuronal cells, their role in 
      the development of AP is largely unknown. We hypothesized that trigeminal ganglia 
      (TG) Nav1.8(+) nociceptors regulate bone metabolism changes in response to AP. A 
      selective ablation of nociceptive neurons in Nav1.8(Cre)/Diphtheria toxin A 
      (DTA)(Lox) mouse line was used to evaluate the development and progression of AP 
      using murine model of infection-induced AP. Ablation of Nav1.8(+) nociceptors had 
      earlier progression of AP with larger osteolytic lesions. Immunohistochemical and 
      RNAscope analyses demonstrated greater number of macrophages, T-cells, osteoclast 
      and osteoblast precursors and an increased RANKL:OPG ratio at earlier time points 
      among Nav1.8(Cre)/ DTA(Lox) mice. There was an increased expression of IL-1alpha and 
      IL-6 within lesions of nociceptor-ablated mice. Further, co-culture experiments 
      demonstrated that TG neurons promoted osteoblast mineralization and inhibited 
      osteoclastic function. The findings suggest that TG Nav1.8(+) neurons contribute 
      to modulation of the AP development by delaying the influx of immune cells, 
      promoting osteoblastic differentiation, and decreasing osteoclastic activities. 
      This newly uncovered mechanism could become a therapeutic strategy for the 
      treatment of AP and minimize the persistence of osteolytic lesions in refractory 
      cases.
CI  - (c) 2022. The Author(s).
FAU - Austah, Obadah N
AU  - Austah ON
AD  - Department of Endodontics, University of Texas Health Science Center at San 
      Antonio, 7703 Floyd Curl Dr, San Antonio, TX, 78229, USA.
AD  - Department of Endodontics, Faculty of Dentistry, King Abdulaziz University, 
      Jeddah, Saudi Arabia.
FAU - Lillis, Katherine V
AU  - Lillis KV
AD  - Department of Endodontics, University of Texas Health Science Center at San 
      Antonio, 7703 Floyd Curl Dr, San Antonio, TX, 78229, USA.
FAU - Akopian, Armen N
AU  - Akopian AN
AD  - Department of Endodontics, University of Texas Health Science Center at San 
      Antonio, 7703 Floyd Curl Dr, San Antonio, TX, 78229, USA.
FAU - Harris, Stephen E
AU  - Harris SE
AD  - Department of Periodontics, University of Texas Health Science Center at San 
      Antonio, San Antonio, TX, USA.
FAU - Grinceviciute, Ruta
AU  - Grinceviciute R
AD  - Department of Endodontics, University of Texas Health Science Center at San 
      Antonio, 7703 Floyd Curl Dr, San Antonio, TX, 78229, USA.
FAU - Diogenes, Anibal
AU  - Diogenes A
AUID- ORCID: 0000-0001-5081-8060
AD  - Department of Endodontics, University of Texas Health Science Center at San 
      Antonio, 7703 Floyd Curl Dr, San Antonio, TX, 78229, USA. diogenes@uthscsa.edu.
LA  - eng
GR  - R01 DE027929/DE/NIDCR NIH HHS/United States
GR  - R01DE027929/DE/NIDCR NIH HHS/United States
PT  - Journal Article
DEP - 20220531
PL  - Switzerland
TA  - Cell Mol Life Sci
JT  - Cellular and molecular life sciences : CMLS
JID - 9705402
SB  - IM
MH  - Animals
MH  - Cell Communication
MH  - Mice
MH  - Nociceptors/metabolism
MH  - *Osteocytes
MH  - *Periapical Periodontitis/metabolism
MH  - Sensory Receptor Cells
PMC - PMC9156470
OTO - NOTNLM
OT  - Bone
OT  - Nav1.8
OT  - Neurons
OT  - Nociceptor
OT  - Osteolytic
OT  - Sensory
COIS- The authors have no relevant financial or non-financial interests to disclose.
EDAT- 2022/06/01 06:00
MHDA- 2022/06/03 06:00
PMCR- 2022/05/31
CRDT- 2022/05/31 15:35
PHST- 2022/03/21 00:00 [received]
PHST- 2022/04/28 00:00 [accepted]
PHST- 2022/04/24 00:00 [revised]
PHST- 2022/05/31 15:35 [entrez]
PHST- 2022/06/01 06:00 [pubmed]
PHST- 2022/06/03 06:00 [medline]
PHST- 2022/05/31 00:00 [pmc-release]
AID - 10.1007/s00018-022-04335-w [pii]
AID - 4335 [pii]
AID - 10.1007/s00018-022-04335-w [doi]
PST - epublish
SO  - Cell Mol Life Sci. 2022 May 31;79(6):330. doi: 10.1007/s00018-022-04335-w.