Overexpression of RPN2 promotes osteogenic differentiation of hBMSCs through the JAK/STAT3 pathway.

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Tytuł:: Overexpression of RPN2 promotes osteogenic differentiation of hBMSCs through the JAK/STAT3 pathway.
Autorzy:: Ni L; Department of Geriatrics, Yangpu District Shidong Hospital, Shanghai, China.
Yu J; Department of Geriatrics, Yangpu District Shidong Hospital, Shanghai, China.
Gui X; Department of Geriatrics, Yangpu District Shidong Hospital, Shanghai, China.
Lu Z; Department of Geriatrics, Yangpu District Shidong Hospital, Shanghai, China.
Wang X; Department of Geriatrics, Yangpu District Shidong Hospital, Shanghai, China.
Guo H; Department of Geriatrics, Yangpu District Shidong Hospital, Shanghai, China.
Zhou Y; Department of Geriatrics, Yangpu District Shidong Hospital, Shanghai, China.
Źródło:: FEBS open bio [FEBS Open Bio] 2020 Jan; Vol. 10 (1), pp. 158-167. Date of Electronic Publication: 2019 Dec 14.
Typ publikacji:: Journal Article
Język:: English
Imprint Name(s):: Publication: Jan. 2016- : West Sussex : John Wiley & Sons Ltd.
Original Publication: Amsterdam : Elsevier, 2011-
MeSH Terms:: Cell Differentiation*/genetics
Osteogenesis*/genetics
Hexosyltransferases/*metabolism
Janus Kinase 1/*metabolism
Mesenchymal Stem Cells/*metabolism
Proteasome Endopeptidase Complex/*metabolism
STAT3 Transcription Factor/*metabolism
Cells, Cultured ; Hexosyltransferases/genetics ; Humans ; Janus Kinase 1/genetics ; Mesenchymal Stem Cells/cytology ; Proteasome Endopeptidase Complex/genetics ; Ubiquitination
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Contributed Indexing:: Keywords: JAK/STAT3; RPN2; bone mesenchymal stem cell; hBMSC; osteogenic differentiation
Substance Nomenclature:: 0 (STAT3 Transcription Factor)
0 (STAT3 protein, human)
EC 2.4.1.- (Hexosyltransferases)
EC 2.4.99.18 (RPN2 protein, human)
EC 2.7.10.2 (JAK1 protein, human)
EC 2.7.10.2 (Janus Kinase 1)
EC 3.4.25.1 (Proteasome Endopeptidase Complex)
Entry Date(s):: Date Created: 20191120 Date Completed: 20210104 Latest Revision: 20210104
Update Code:: 20240104
PubMed Central ID:: PMC6943221
DOI:: 10.1002/2211-5463.12766
PMID:: 31743606
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Osteoporosis is characterized by decreased bone mass and degenerating bone structure, which cause severe bone fragility and increase the risk for fractures. Human bone mesenchymal stem cells (hBMSCs) differentiate into osteoblasts through osteogenesis, and disturbances in the balance between bone generation and degeneration underlie the pathogenesis of senile osteoporosis. The highly conserved glycoprotein Ribophorin II (RPN2) is involved in multiple biological reactions, but the role of RPN2 in the osteogenic differentiation of hBMSCs and their molecular etiology is incompletely understood. Here, we show that RPN2 expression is up-regulated in hBMSCs during osteogenic differentiation. In vitro assays revealed that silencing of RPN2 inhibited hBMSC differentiation into osteoblasts. Moreover, RPN2 overexpression enhanced the expression of linked genes and resulted in high alkaline phosphatase activity. Our results suggest that RPN2 targets Janus kinase 1 (JAK1), and RPN2 overexpression was observed to induce JAK1 ubiquitination. Depletion of JAK1 facilitated osteogenic differentiation of RPN2-silenced hBMSCs. Moreover, western blot analysis revealed that RPN2 silencing suppressed the stimulation and nuclear translocation of the downstream signal transducer and activator of transcription 3 sensor; this could be reversed via RPN2 overexpression. This research sheds light on an innovative molecular mechanism that is associated with hBMSC differentiation into osteoblasts and may facilitate bone anabolism through RPN2.
(© 2019 The Authors. Published by FEBS Press and John Wiley & Sons Ltd.)

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