Abstract
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.
Highlights
Osteoporosis is characterized by decreased bone mass and degenerating bone structure, which cause severe bone fragility and increase the risk for fractures
Regulation of ribophorin II (RPN2) expression mediates the osteogenic differentiation process of human bone mesenchymal stem cell (hBMSC) hBMSCs were first transfected with the RPN2-overexpressing vector to up-regulate cellular RPN2 and to assess the contribution of RPN2 overexpression to hBMSC osteoblastic differentiation
The results of this study indicate that RPN2 is a novel promoter of osteogenic differentiation of hBMSCs, which confirms that with Janus kinase 1 (JAK1) and signal transducers and activators of transcription (STAT3) pathways as a target, overexpression of RPN2 can increase ubiquitination of JAK1 and lead to blockage of the JAK1/STAT3 pathway
Summary
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. Depletion of JAK1 facilitated osteogenic differentiation of RPN2-silenced hBMSCs. 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. Abbreviations ALP, alkaline phosphatase; BMP, bone morphogenetic protein; DAPI, 4’,6-diamidine-2’-phenylindole dihydrochloride; CdCl2, cadmium chloride; hAS, human allogeneic serum; hBMSC, human bone mesenchymal stem cell; JAK1, Janus kinase 1; NC, negative control; NCi, negative control siRNA; PFA, paraformaldehyde; qRT-PCR, quantitative RT-PCR; RPN2, ribophorin II; SD, standard deviation; STAT3, signal transducers and activators of transcription; WB, western blotting. Its role in the osteogenic differentiation of hBMSCs in senile osteoporosis has not been probed
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