Dihydroartemisinin Promotes the Osteogenesis of Human Mesenchymal Stem Cells via the ERK and Wnt/<i>β</i>-Catenin Signaling Pathways

Ni, Licheng; Kuang, Zhihui; Gong, Zhe; Xue, Deting; Zheng, Qiang

doi:10.1155/2019/3456719

Cited by 18 publications

(17 citation statements)

References 29 publications

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“…Extracellular signal-regulated kinase (ERK) pathway, also known as the Ras-Raf-MEK-ERK pathway, is involved in a variety of physiological processes such as cell proliferation, division, and survival [34,35]. Numerous studies have revealed that ERK signaling pathway plays vital roles in the osteogenic differentiation [36][37][38][39]. With regard to the relationship between HSPB7 and ERK signaling pathway, Naderi found HSPB7 overexpression in breast cancer cells reduced the level of p-ERK [18].…”

Section: Discussionmentioning

confidence: 99%

HSPB7 regulates osteogenic differentiation of human adipose derived stem cells via ERK signaling pathway

2020

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Background Heat shock protein B7 (HSPB7), which belongs to small heat shock protein family, has been reported to be involved in diverse biological processes and diseases. However, whether HSPB7 regulates osteogenic differentiation of human adipose derived stem cells (hASCs) remains unexplored. Methods The expression level of HSPB7 during the osteogenesis of hASCs was examined by quantitative reverse transcription polymerase chain reaction (qRT-PCR) and Western blot analysis. Lentivirus transfection was used to knock down or overexpress HSPB7, which enabled us to investigate the effect of HSPB7 on osteogenic differentiation of hASCs. U0126 and extracellular signal-regulated protein kinase 1/2 (ERK1/2) siRNA were used to identify the mechanism of the HSPB7/ERK1/2 axis in regulating osteogenic differentiation of hASCs. Moreover, ectopic bone formation in nude mice and osteoporosis mice model was used to investigate the effect of HSPB7 on osteogenesis in vivo. Results In this study, we found the expression of HSPB7 was significantly downregulated during the osteogenic differentiation of hASCs. HSPB7 knockdown remarkably promoted osteogenic differentiation of hASCs, while HSPB7 overexpression suppressed osteogenic differentiation of hASCs both in vitro and in vivo. Moreover, we discovered that the enhancing effect of HSPB7 knockdown on osteogenic differentiation was related to the activation of extracellular signal-regulated protein kinase (ERK) signaling pathway. Inhibition of ERK signaling pathway with U0126 or silencing ERK1/2 effectively blocked the stimulation of osteogenic differentiation induced by HSPB7 knockdown. Additionally, we found that HSPB7 expression was markedly increased in mouse bone marrow mesenchymal stem cells (mBMSCs) from the osteoporotic mice which suggested that HSPB7 might be utilized as a potential target in the development of effective therapeutic strategies to treat osteoporosis and other bone diseases. Conclusion Taken together, these findings uncover a previously unrecognized function of HSPB7 in regulating osteogenic differentiation of hASCs, partly via the ERK signaling pathway.

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Section: Discussionmentioning

confidence: 99%

HSPB7 regulates osteogenic differentiation of human adipose derived stem cells via ERK signaling pathway

2020

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“…APC was predicted as the potential target of miR-675 ( Figure 5A). APC is a negative regulator in the activation of Wnt/β-catenin pathway, which is closely related to the osteogenesis of MSCs [21,22]. Western blot results proved that APC was significantly decreased by miR-675 mimics and increased by miR-675 inhibitor.…”

Section: Mir-675 Targets Apc and Downregulates Apc Expression In Hamscsmentioning

confidence: 91%

Human amnion-derived mesenchymal stem cells promote osteogenic differentiation of human bone marrow mesenchymal stem cells via H19/miR-675/APC axis

Bian

Yuan

et al. 2020

Aging

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Bone volume inadequacy is an emerging clinical problem impairing the feasibility and longevity of dental implants. Human bone marrow mesenchymal stem cells (HBMSCs) have been widely used in bone remodeling and regeneration. This study examined the effect of long noncoding RNAs (lncRNAs)-H19 on the human amnion-derived mesenchymal stem cells (HAMSCs)-droved osteogenesis in HBMSCs. HAMSCs and HBMSCs were isolated from abandoned amniotic membrane samples and bone marrow. The coculture system was conducted using transwells, and H19 level was measured by quantitative real-time reverse transcriptionpolymerase chain reaction (RT-PCR). The mechanism was further verified. We here discovered that osteogenesis of HBMSCs was induced by HAMSCs, while H19 level in HAMSCs was increased during coculturing. H19 had no significant effect on the proliferative behaviors of HBMSCs, while its overexpression of H19 in HAMSCs led to the upregulated osteogenesis of HBMSCs in vivo and in vitro; whereas its knockdown reversed these effects. Mechanistically, H19 promoted miR-675 expression and contributed to the competitively bounding of miR-675 and Adenomatous polyposis coli (APC), thus significantly activating the Wnt/β-catenin pathway. The results suggested that HAMSCs promote osteogenic differentiation of HBMSCs via H19/miR-675/APC pathway, and supply a potential target for the therapeutic treatment of bone-destructive diseases.

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“…As APC is a negative regulator in the Wnt/β-catenin pathway [ 27 ], APC overexpression was established in HBMSCs and the cells were assigned to the following groups: NC: HAMSCs + LPS + HBMSCs APC NC ; APC: HAMSCs + LPS + HBMSCs APC . Western blot analysis showed that APC overexpression increased the protein level of APC and decreased the protein level of β-catenin (Fig.…”

Section: Resultsmentioning

confidence: 99%

Human amnion-derived mesenchymal stem cells promote osteogenic differentiation of lipopolysaccharide-induced human bone marrow mesenchymal stem cells via ANRIL/miR-125a/APC axis

Wang

Huang

et al. 2021

Stem Cell Res Ther

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Background and aim Periodontitis is a chronic inflammatory disease inducing the absorption of alveolar bone and leading to tooth loss. Human amnion-derived mesenchymal stem cells (HAMSCs) have been used for studying inflammatory processes. This study aimed to explore the role of long noncoding RNA (lncRNA) antisense noncoding RNA in the INK4 locus (ANRIL) in HAMSC-driven osteogenesis in lipopolysaccharide (LPS)-induced human bone marrow mesenchymal stem cells (HBMSCs). Methods The cells were incubated with a co-culture system. Reactive oxygen species (ROS) level and superoxide dismutase (SOD) activity were used to detect the oxidative stress level. Flow cytometry was performed to determine cell proliferation. The alkaline phosphatase (ALP) activity, Alizarin red assay, cell transfection, and rat mandibular defect model were used to evaluate the osteogenic differentiation. Quantitative real-time reverse transcription–polymerase chain reaction (RT-PCR), Western blot analysis, dual-luciferase reporter assay, and immunofluorescence staining were used to evaluate the molecular mechanisms. Results This study showed that HAMSCs promoted the osteogenesis of LPS-induced HBMSCs, while the ANRIL level in HBMSCs decreased during co-culture. ANRIL had no significant influence on the proliferation of LPS-induced HBMSCs. However, its overexpression inhibited the HAMSC-driven osteogenesis in vivo and in vitro, whereas its knockdown reversed these effects. Mechanistically, this study found that downregulating ANRIL led to the overexpression of microRNA-125a (miR-125a), and further contributed to the competitive binding of miR-125a and adenomatous polyposis coli (APC), thus significantly activating the Wnt/β-catenin pathway. Conclusion The study indicated that HAMSCs promoted the osteogenic differentiation of LPS-induced HBMSCs via the ANRIL/miR-125a/APC axis, and offered a novel approach for periodontitis therapy.

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Dihydroartemisinin Promotes the Osteogenesis of Human Mesenchymal Stem Cells via the ERK and Wnt/β-Catenin Signaling Pathways

Cited by 18 publications

References 29 publications

HSPB7 regulates osteogenic differentiation of human adipose derived stem cells via ERK signaling pathway

HSPB7 regulates osteogenic differentiation of human adipose derived stem cells via ERK signaling pathway

Human amnion-derived mesenchymal stem cells promote osteogenic differentiation of human bone marrow mesenchymal stem cells via H19/miR-675/APC axis

Human amnion-derived mesenchymal stem cells promote osteogenic differentiation of lipopolysaccharide-induced human bone marrow mesenchymal stem cells via ANRIL/miR-125a/APC axis

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