Dental pulp-derived stem cells inhibit osteoclast differentiation by secreting osteoprotegerin and deactivating AKT signalling in myeloid cells.
Animals
Biomarkers
Cell Differentiation
Cells, Cultured
Coculture Techniques
Dental Pulp
/ cytology
Gene Expression Regulation
Humans
Inflammation Mediators
Mice
Myeloid Cells
/ cytology
Osteoclasts
/ cytology
Osteoprotegerin
/ biosynthesis
Proto-Oncogene Proteins c-akt
/ metabolism
RAW 264.7 Cells
Signal Transduction
Stem Cells
/ cytology
Stress, Physiological
M2 polarization
dental pulp-derived stem cells
osteoclast differentiation
osteoprotegerin
pAKT
Journal
Journal of cellular and molecular medicine
ISSN: 1582-4934
Titre abrégé: J Cell Mol Med
Pays: England
ID NLM: 101083777
Informations de publication
Date de publication:
03 2021
03 2021
Historique:
pubmed:
30
1
2021
medline:
22
9
2021
entrez:
29
1
2021
Statut:
ppublish
Résumé
Osteoclasts (OCs) differentiate from the monocyte/macrophage lineage, critically regulate bone resorption and remodelling in both homeostasis and pathology. Various immune and non-immune cells help initiating activation of myeloid cells for differentiation, whereas hyper-activation leads to pathogenesis, and mechanisms are yet to be completely understood. Herein, we show the efficacy of dental pulp-derived stem cells (DPSCs) in limiting RAW 264.7 cell differentiation and underlying molecular mechanism, which has the potential for future therapeutic application in bone-related disorders. We found that DPSCs inhibit induced OC differentiation of RAW 264.7 cells when co-cultured in a contact-free system. DPSCs reduced expression of key OC markers, such as NFATc1, cathepsin K, TRAP, RANK and MMP-9 assessed by quantitative RT-PCR, Western blotting and immunofluorescence detection methods. Furthermore, quantitative RT-PCR analysis revealed that DPSCs mediated M2 polarization of RAW 264.7 cells. To define molecular mechanisms, we found that osteoprotegerin (OPG), an OC inhibitory factor, was up-regulated in RAW 264.7 cells in the presence of DPSCs. Moreover, DPSCs also constitutively secrete OPG that contributed in limiting OC differentiation. Finally, the addition of recombinant OPG inhibited OC differentiation in a dose-dependent manner by reducing the expression of OC differentiation markers, NFATc1, cathepsin K, TRAP, RANK and MMP9 in RAW 264.7 cells. RNAKL and M-CSF phosphorylate AKT and activate PI3K-AKT signalling pathway during osteoclast differentiation. We further confirmed that OPG-mediated inhibition of the downstream activation of PI3K-AKT signalling pathway was similar to the DPSC co-culture-mediated inhibition of OC differentiation. This study provides novel evidence of DPSC-mediated inhibition of osteoclastogenesis mechanisms.
Identifiants
pubmed: 33511706
doi: 10.1111/jcmm.16071
pmc: PMC7933945
doi:
Substances chimiques
Biomarkers
0
Inflammation Mediators
0
Osteoprotegerin
0
Proto-Oncogene Proteins c-akt
EC 2.7.11.1
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
2390-2403Subventions
Organisme : NEI NIH HHS
ID : 1R41EY024217
Pays : United States
Organisme : NIAMS NIH HHS
ID : R01 AR068279
Pays : United States
Organisme : NIA NIH HHS
ID : R41 AG057242
Pays : United States
Organisme : NIAMS NIH HHS
ID : R01AR068279
Pays : United States
Organisme : NEI NIH HHS
ID : R41 EY024217
Pays : United States
Organisme : NIA NIH HHS
ID : 1R41AG057242
Pays : United States
Informations de copyright
© 2021 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.
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