PI3K-Akt signaling regulates BMP2-induced osteogenic differentiation of mesenchymal stem cells (MSCs): A transcriptomic landscape analysis

Gao, Shengqiang; Chen, Bowen; Zhu, Zhenglin; Du, Chengcheng; Zou, Jing; Yang, Yunfei; Huang, Wei; Liao, Junyi

doi:10.1016/j.scr.2022.103010

Cited by 8 publications

(9 citation statements)

References 51 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The circular plot of GO enrichment revealed that the top 25 expressed miRNAs were related to the nucleoplasm, chromatin, and cytosol in cellular components, transcription, protein phosphorylation, and angiogenesis in biological processes, and protein binding, transcriptional activator activity, and transcription factor activity in molecular functions (Figure 6b). KEGG enrichment analysis revealed that the target genes were enriched in signaling pathways responsible for osteoblast differentiation (FoxO signaling pathway), 59 osteogenic differentiation of stem cells (MAPK and PI3K-Akt signaling pathways), 60 and cell-fate determination (cellular senescence and Ras signaling pathway) (Figure S6).…”

Section: Resultsmentioning

confidence: 99%

Osteoinductive Dental Pulp Stem Cell-Derived Extracellular Vesicle-Loaded Multifunctional Hydrogel for Bone Regeneration

Wang,

Wei,

et al. 2024

ACS Nano

View full text Add to dashboard Cite

Stem cell-derived extracellular vesicles (EVs) show great potential for promoting bone tissue regeneration. However, normal EVs (Nor-EVs) have a limited ability to direct tissue-specific regeneration. Therefore, it is necessary to optimize the osteogenic capacity of EV-based systems for repairing extensive bone defects. Herein, we show that hydrogels loaded with osteoinductive dental pulp stem cellderived EVs (Ost-EVs) enhanced bone tissue remodeling, resulting in a 2.23 ± 0.25-fold increase in the expression of bone morphogenetic protein 2 (BMP2) compared to the hydrogel control group. Moreover, Ost-EVs led to a higher expression of alkaline phosphatase (ALP) (1.88 ± 0.16 of Ost-EVs relative to Nor-EVs) and the formation of orange-red calcium nodules (1.38 ± 0.10 of Ost-EVs relative to Nor-EVs) in vitro. RNA sequencing revealed that Ost-EVs showed significantly high miR-1246 expression. An ideal hydrogel implant should also adhere to surrounding moist tissues. In this study, we were drawn to mussel-inspired adhesive modification, where the hydrogel carrier was crafted from hyaluronic acid (HA) and polyethylene glycol derivatives, showcasing impressive tissue adhesion, self-healing capabilities, and the ability to promote bone growth. The modified HA (mHA) hydrogel was also responsive to environmental stimuli, making it an effective carrier for delivering EVs. In an ectopic osteogenesis animal model, the Ost-EV/hydrogel system effectively alleviated inflammation, accelerated revascularization, and promoted tissue mineralization. We further used a rat femoral condyle defect model to evaluate the in situ osteogenic ability of the Ost-EVs/hydrogel system. Collectively, our results suggest that Ost-EVs combined with biomaterial-based hydrogels hold promising potential for treating bone defects.

show abstract

Section: Resultsmentioning

confidence: 99%

Osteoinductive Dental Pulp Stem Cell-Derived Extracellular Vesicle-Loaded Multifunctional Hydrogel for Bone Regeneration

Wang,

Wei,

et al. 2024

ACS Nano

View full text Add to dashboard Cite

show abstract

“…Rap1 has been shown to regulate the fate of calvarial mesenchymal cells, as it promotes chondrogenesis, while its depletion results in osteogenesis [ 170 ]. The PI3K-Akt signaling pathway has been reported to be involved in the differentiation process of mesenchymal cells toward the osteogenic lineage [ 171 ].…”

Section: Discussionmentioning

confidence: 99%

A Simplified and Effective Approach for the Isolation of Small Pluripotent Stem Cells Derived from Human Peripheral Blood

et al. 2023

View full text Add to dashboard Cite

Pluripotent stem cells are key players in regenerative medicine. Embryonic pluripotent stem cells, despite their significant advantages, are associated with limitations such as their inadequate availability and the ethical dilemmas in their isolation and clinical use. The discovery of very small embryonic-like (VSEL) stem cells addressed the aforementioned limitations, but their isolation technique remains a challenge due to their small cell size and their efficiency in isolation. Here, we report a simplified and effective approach for the isolation of small pluripotent stem cells derived from human peripheral blood. Our approach results in a high yield of small blood stem cell (SBSC) population, which expresses pluripotent embryonic markers (e.g., Nanog, SSEA-3) and the Yamanaka factors. Further, a fraction of SBSCs also co-express hematopoietic markers (e.g., CD45 and CD90) and/or mesenchymal markers (e.g., CD29, CD105 and PTH1R), suggesting a mixed stem cell population. Finally, quantitative proteomic profiling reveals that SBSCs contain various stem cell markers (CD9, ITGA6, MAPK1, MTHFD1, STAT3, HSPB1, HSPA4), and Transcription reg complex factors (e.g., STAT5B, PDLIM1, ANXA2, ATF6, CAMK1). In conclusion, we present a novel, simplified and effective isolating process that yields an abundant population of small-sized cells with characteristics of pluripotency from human peripheral blood.

show abstract

“…In a similar manner, circRNA_0016624 can reportedly interact with miR‐98 to induce the enhanced expression of the key regulator of osteogenesis BMP2 (bone morphogenetic protein 2), thus promoting the differentiation of osteoblasts 33 . BMP2 belongs to the transforming growth factor β (TGF‐β) superfamily and has been shown to induce osteogenic differentiation of MSCs 34,35 . The association between circRNA_0016624 and BMP2 indicates that circRNAs can act as a key regulators of osteogenic differentiation.…”

Section: Role Of Circrnas In Osteogenic Differentiationmentioning

confidence: 97%

“…33 BMP2 belongs to the transforming growth factor β (TGF-β) superfamily and has been shown to induce osteogenic differentiation of MSCs. 34,35 The association between circRNA_0016624 and BMP2 indicates that circRNAs can act as a key regulators of osteogenic differentiation.…”

Section: Circrnas As Regulators Of Bm Mesenchymal Stem Cell Different...mentioning

confidence: 99%

Roles of circular RNAs in osteogenic/osteoclastogenic differentiation

Wang

Zhang

et al. 2023

BioFactors

View full text Add to dashboard Cite

The process of bone remodeling occurs and is regulated through interactions between osteoclasts, which resorb bone, and osteoblasts, which generate bone tissue. When the homeostatic balance between these two cell types is dysregulated, this can contribute to abnormal bone remodeling resulting in a loss of bone mass as is observed in osteoporosis (OP) and other forms of degenerative bone metabolic diseases. At present, details of molecular mechanism underlying the development of bone metabolic diseases such as OP remain to be elucidated. Circular RNAs (circRNAs) are small non‐coding RNA molecules with a closed‐loop structure that can regulate the differentiation of osteoclasts and osteoblasts. The present review provides a systematic overview of recent literature on the processes through which circRNAs regulate the dynamic balance between osteoblasts and osteoclasts that ultimately preserve bone homeostasis. It will also give insight that can shape current understanding of the pathogenesis of OP and other bone metabolic diseases to better guide diagnostic and treatment strategies for affected patients.

show abstract

PI3K-Akt signaling regulates BMP2-induced osteogenic differentiation of mesenchymal stem cells (MSCs): A transcriptomic landscape analysis

Cited by 8 publications

References 51 publications

Osteoinductive Dental Pulp Stem Cell-Derived Extracellular Vesicle-Loaded Multifunctional Hydrogel for Bone Regeneration

Osteoinductive Dental Pulp Stem Cell-Derived Extracellular Vesicle-Loaded Multifunctional Hydrogel for Bone Regeneration

A Simplified and Effective Approach for the Isolation of Small Pluripotent Stem Cells Derived from Human Peripheral Blood

Roles of circular RNAs in osteogenic/osteoclastogenic differentiation

Contact Info

Product

Resources

About