PMID- 36725746
OWN - NLM
STAT- MEDLINE
DCOM- 20231027
LR  - 20231027
IS  - 1573-4978 (Electronic)
IS  - 0301-4851 (Linking)
VI  - 50
IP  - 4
DP  - 2023 Apr
TI  - Low concentrations of tumor necrosis factor-alpha promote human periodontal 
      ligament stem cells osteogenic differentiation by activation of autophagy via 
      inhibition of AKT/mTOR pathway.
PG  - 3329-3339
LID - 10.1007/s11033-022-08173-8 [doi]
AB  - BACKGROUND: Tumor necrosis factor-alpha (TNF-alpha) is one of the crucial 
      inflammatory factors in alveolar bone metabolism during the process of 
      periodontitis. Autophagy is indispensable for proper osteoblast function. 
      However, the effects of autophagy on osteogenic differentiation of human 
      periodontal ligament stem cells (hPDLSCs) in inflammatory microenvironment and 
      the underlying mechanisms remain to be clarified. The aim of the present study 
      was to investigate whether autophagy participates in hPDLSCs differentiation 
      after treated with TNF-alpha and explore the underlying mechanisms. METHODS AND 
      RESULTS: Characterizations of hPDLSCs were evaluated by Alizarin-red S staining, 
      Oil red staining and flow cytometry. hPDLSCs were treated with various 
      concentrations of TNF-alpha. Rapamycin or 3MA was used to achieve or inhibit 
      autophagy activation. AKT signaling was inhibited using ARQ092. Cell 
      proliferation was evaluated using Cell Counting Kit-8 (CCK8) assay. Real-time 
      reverse transcriptase-polymerase chain reaction assay (RT-PCR), western blot, 
      alkaline phosphatase (ALP) staining and Alizarin Red S staining were applied to 
      evaluate levels of osteogenic differentiation and autophagy. CCK8 showed that low 
      concentrations of TNF-alpha had no influence on cell proliferation, while high 
      concentrations of TNF-alpha inhibited proliferation. Low concentrations of TNF-alpha 
      promoted osteogenic differentiation and autophagy, while high concentrations of 
      TNF-alpha inhibited osteogenic differentiation and autophagy in hPDLSCs. The levels 
      of osteogenic differentiation in hPDLSCs were partly effected after co-incubation 
      with 0.1 ng/mL TNF-alpha with 3MA or Rapamycin. ARQ092 enhanced 0.1 ng/mL 
      TNF-alpha-induced ALP expression and mineral nodule formation. CONCLUSION: Low 
      concentrations of TNF-alpha promote hPDLSCs osteogenic differentiation by activation 
      of autophagy via inhibition of AKT/mTOR signaling.
CI  - (c) 2023. The Author(s), under exclusive licence to Springer Nature B.V.
FAU - Yuping, Qi
AU  - Yuping Q
AUID- ORCID: 0000-0002-8921-6320
AD  - Department of Oral Medicine, Qilu Hospital of Shandong University, Wenhua West 
      Road 107, 250012, Jinan, China.
AD  - Institute of Stomatology, Shandong University, Jinan, China.
FAU - Yijun, Luan
AU  - Yijun L
AUID- ORCID: 0000-0002-6590-9229
AD  - Department of Oral Medicine, Qilu Hospital of Shandong University, Wenhua West 
      Road 107, 250012, Jinan, China.
AD  - Institute of Stomatology, Shandong University, Jinan, China.
FAU - Limei, Wang
AU  - Limei W
AUID- ORCID: 0000-0002-5041-2287
AD  - Department of Oral Medicine, Qilu Hospital of Shandong University, Wenhua West 
      Road 107, 250012, Jinan, China. sdkqwlm@163.com.
AD  - Institute of Stomatology, Shandong University, Jinan, China. sdkqwlm@163.com.
LA  - eng
GR  - ZR2019BH081/Natural Science Foundation of Shandong Province/
PT  - Journal Article
DEP - 20230201
PL  - Netherlands
TA  - Mol Biol Rep
JT  - Molecular biology reports
JID - 0403234
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - 0 (Tumor Necrosis Factor-alpha)
SB  - IM
MH  - Humans
MH  - Cell Differentiation/genetics
MH  - Cell Proliferation
MH  - Cells, Cultured
MH  - *Osteogenesis/genetics
MH  - *Periodontal Ligament/metabolism
MH  - *Proto-Oncogene Proteins c-akt/genetics/metabolism
MH  - *Stem Cells
MH  - *TOR Serine-Threonine Kinases/genetics/metabolism
MH  - *Tumor Necrosis Factor-alpha/genetics/metabolism
MH  - Autophagy/genetics
OTO - NOTNLM
OT  - AKT/mTOR pathway
OT  - Autophagy
OT  - Osteogenic differentiation
OT  - TNF-alpha
OT  - hPDLSCs
EDAT- 2023/02/02 06:00
MHDA- 2023/03/29 06:05
CRDT- 2023/02/01 23:14
PHST- 2022/07/29 00:00 [received]
PHST- 2022/12/01 00:00 [accepted]
PHST- 2023/03/29 06:05 [medline]
PHST- 2023/02/02 06:00 [pubmed]
PHST- 2023/02/01 23:14 [entrez]
AID - 10.1007/s11033-022-08173-8 [pii]
AID - 10.1007/s11033-022-08173-8 [doi]
PST - ppublish
SO  - Mol Biol Rep. 2023 Apr;50(4):3329-3339. doi: 10.1007/s11033-022-08173-8. Epub 
      2023 Feb 1.