Hedgehog Activation Regulates Human Osteoblastogenesis

Onodera, Shin; Saito, Akiko; Hojo, Hironori; Nakamura, Takashi; Zujur, Denise; Watanabe, Kiichi; Morita, Nana; Hasegawa, Daigo; Hara, Masaki; Nakauchi, Hiromitsu; Nomura, Takeshi; Shibahara, Takahiko; Yamaguchi, Akira; Chung, Ung‐il; Ohba, Shinsuke

doi:10.1016/j.stemcr.2020.05.008

Cited by 18 publications

(15 citation statements)

References 44 publications

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“…GO analysis of target genes of this network showed that "mRNA translation and transport" was the most significant biological function in hBMSCs (Figure 6B). In addition, "p53 signaling pathway" and "Hedgehog signaling pathway" were significantly enriched, which have also been suggested to play important roles in osteogenesis (Tyner et al, 2002;Onodera et al, 2020) (Figure 6C). These results further suggested that both lncRNAs and circRNAs could act as miRNA sponge to regulate the expression of downstream genes, which in turn take part in osteogenic differentiation of BMSCs.…”

Section: Construction and Analyses Of Cerna Networkmentioning

confidence: 88%

Systematic Analysis of mRNAs and ncRNAs in BMSCs of Senile Osteoporosis Patients

Geng¹,

Chen²,

Chang³

et al. 2021

Front. Genet.

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Senile osteoporosis (SOP) is a worldwide age-related disease characterized by the loss of bone mass and decrease in bone strength. Bone mesenchymal stem cells (BMSCs) play an important role in the pathology of senile osteoporosis. Abnormal expression and regulation of non-coding RNA (ncRNA) are involved in a variety of human diseases. In the present study, we aimed to identify differentially expressed mRNAs and ncRNAs in senile osteoporosis patient-derived BMSCs via high-throughput transcriptome sequencing in combination with bioinformatics analysis. As a result, 415 mRNAs, 30 lncRNAs, 6 circRNAs and 27 miRNAs were found to be significantly changed in the senile osteoporosis group. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were applied to analyze the function of differentially expressed mRNAs and ncRNAs. The circRNA–miRNA–mRNA regulatory network was constructed using the cytoHubba plugin based on the Cytoscape software. Interestingly, circRNA008876-miR-150-5p-mRNA was the sole predicted circRNA-miRNA-mRNA network. The differential expression profile of this ceRNA network was further verified by qRT-PCR. The biological function of this network was validated by overexpression and knockdown experiments. In conclusion, circRNA008876-miR-150-5p-mRNA could be an important ceRNA network involved in senile osteoporosis, which provides potential biomarkers and therapeutic targets for senile osteoporosis.

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Section: Construction and Analyses Of Cerna Networkmentioning

confidence: 88%

Systematic Analysis of mRNAs and ncRNAs in BMSCs of Senile Osteoporosis Patients

Geng¹,

Chen²,

Chang³

et al. 2021

Front. Genet.

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“…The conversion of full-length Gli3 (usually considered as pro-osteogenic) to repressed Gli3 was shown to be reduced not only in Ptch1 +/− mice but also in GS patient-derived induced pluripotent stem (iPS) cells. This inhibitory Gli3 competes with Runx2, a master transcription factor for osteoblast differentiation, for DNA binding, suppresses Runx2 function, and reduces bone formation [ 46 , 48 ].…”

Section: Bone Metabolism Hedgehog Over-activation and Pathologicamentioning

confidence: 99%

“…Patient-derived hiPSCs are also used for in vitro disease modeling and drug screening. Recently, iPSCs derived from patients with GS have been reported by several groups [ 31 , 48 , 117 , 118 , 119 , 120 ]. By using iPSCs derived from patients with GS, a model of abnormal tissue development and tumor formation can be constructed.…”

Section: Disease-specific Induced Pluripotent Stem Cellsmentioning

confidence: 99%

Gorlin Syndrome: Recent Advances in Genetic Testing and Molecular and Cellular Biological Research

Onodera

Nakamura

2020

IJMS

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Gorlin syndrome is a skeletal disorder caused by a gain of function mutation in Hedgehog (Hh) signaling. The Hh family comprises of many signaling mediators, which, through complex mechanisms, play several important roles in various stages of development. The Hh information pathway is essential for bone tissue development. It is also the major driver gene in the development of basal cell carcinoma and medulloblastoma. In this review, we first present the recent advances in Gorlin syndrome research, in particular, the signaling mediators of the Hh pathway and their functions at the genetic level. Then, we discuss the phenotypes of mutant mice and Hh signaling-related molecules in humans revealed by studies using induced pluripotent stem cells.

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“…Hedgehog signaling pathway is a conservative and important signaling pathway that participates in various biological metabolism processes in the body [ 23 ]. Studies have shown that the Hedgehog signaling pathway is involved in metabolic processes such as bone formation, metabolism and fracture healing [ 23 , 24 ]. Inhibition of the Hedgehog pathway can lead to fracture nonunion or delayed healing [ 25 , 26 ].…”

Section: Discussionmentioning

confidence: 99%

High-purity magnesium pin enhances bone consolidation in distraction osteogenesis via regulating Ptch protein activating Hedgehog-alternative Wnt signaling

Hamushan

Cai

Zhang

et al. 2021

Bioactive Materials

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Magnesium alloys are promising biomaterials for orthopedic implants because of their degradability, osteogenic effects, and biocompatibility. Magnesium has been proven to promote distraction osteogenesis. However, its mechanism of promoting distraction osteogenesis is not thoroughly studied. In this work, a high-purity magnesium pin developed and applied in rat femur distraction osteogenesis. Mechanical test, radiological and histological analysis suggested that high-purity magnesium pin can promote distraction osteogenesis and shorten the consolidation time. Further RNA sequencing investigation found that alternative Wnt signaling was activated. In further bioinformatics analysis, it was found that the Hedgehog pathway is the upstream signaling pathway of the alternative Wnt pathway. We found that Ptch protein is a potential target of magnesium and verified by molecular dynamics that magnesium ions can bind to Ptch protein. In conclusion, HP Mg implants have the potential to enhance bone consolidation in the DO application, and this process might be via regulating Ptch protein activating Hedgehog-alternative Wnt signaling.

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Hedgehog Activation Regulates Human Osteoblastogenesis

Cited by 18 publications

References 44 publications

Systematic Analysis of mRNAs and ncRNAs in BMSCs of Senile Osteoporosis Patients

Systematic Analysis of mRNAs and ncRNAs in BMSCs of Senile Osteoporosis Patients

Gorlin Syndrome: Recent Advances in Genetic Testing and Molecular and Cellular Biological Research

High-purity magnesium pin enhances bone consolidation in distraction osteogenesis via regulating Ptch protein activating Hedgehog-alternative Wnt signaling

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