Low intensity pulsed ultrasound (LIPUS) maintains osteogenic potency by the increased expression and stability of Nanog through spleen tyrosine kinase (Syk) activation.
Animals
Cell Differentiation
/ radiation effects
Gene Expression Regulation, Developmental
/ radiation effects
Mesenchymal Stem Cells
/ metabolism
Mice
Nanog Homeobox Protein
/ genetics
Osteoblasts
/ radiation effects
Osteogenesis
/ genetics
SOXB1 Transcription Factors
/ genetics
Syk Kinase
/ genetics
Ultrasonic Waves
rho-Associated Kinases
/ genetics
Differentiation
Mesenchymal stem cell
Osteoblast
Osteogenesis
Passage
Journal
Cellular signalling
ISSN: 1873-3913
Titre abrégé: Cell Signal
Pays: England
ID NLM: 8904683
Informations de publication
Date de publication:
10 2019
10 2019
Historique:
received:
13
03
2019
revised:
22
05
2019
accepted:
18
06
2019
pubmed:
23
6
2019
medline:
21
8
2020
entrez:
23
6
2019
Statut:
ppublish
Résumé
Mesenchymal stem cells (MSCs) are a powerful tool for cell-based, clinical therapies like bone regeneration. Therapeutic use of cell transplantation requires many cells, however, the expansion process needed to produce large quantities of cells reduces the differentiation potential of MSCs. Here, we examined the protective effects of low intensity pulsed ultrasound (LIPUS) on the maintenance of osteogenic potency. Primary osteoblastic cells were serially passaged between 2 and 12 times with daily LIPUS treatment. We found that LIPUS stimulation maintains osteogenic differentiation capacity in serially passaged cells, as characterized by improved matrix mineralization and Osteocalcin mRNA expression. Decreased expression of Nanog, Sox2, and Msx2, and increased expression of Pparg2 from serial passaging was recovered in LIPUS-stimulated cells. We found that LIPUS stimulation not only increased but also sustained expression of Nanog in primary osteoblasts and ST2 cells, a mouse mesenchymal stromal cell line. Nanog overexpression in serially passaged cells mimicked the recuperative effects of LIPUS on osteogenic potency, highlighting the important role of Nanog in LIPUS stimulation. Additionally, we found that spleen tyrosine kinase (Syk) is an important signaling molecule to induce Nanog expression in LIPUS-stimulated cells. Syk activation was regulated by both Rho-associated kinase 1 (ROCK1) and extracellular ATP in a paracrine manner. Interestingly, the LIPUS-induced increase in Nanog mRNA expression was regulated by ATP-P2X4-Syk Y323 activation, while the improvement of Nanog protein stability was controlled by the ROCK1-Syk Y525/526 pathway. Taken together, these results indicate that LIPUS stimulation recovers and maintains the osteogenic potency of serially passaged cells through a Syk-Nanog axis.
Identifiants
pubmed: 31228531
pii: S0898-6568(19)30141-X
doi: 10.1016/j.cellsig.2019.109345
pii:
doi:
Substances chimiques
Nanog Homeobox Protein
0
SOX2 protein, human
0
SOXB1 Transcription Factors
0
Syk Kinase
EC 2.7.10.2
Rock1 protein, mouse
EC 2.7.11.1
rho-Associated Kinases
EC 2.7.11.1
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
109345Informations de copyright
Copyright © 2019. Published by Elsevier Inc.