TGF‑β1 promotes the osteoinduction of human osteoblasts via the PI3K/AKT/mTOR/S6K1 signalling pathway

Zhang, Zhaodong; Zhang, Xiuzhi; Zhao, Dewei; Liu, Baoyi; Wang, Benjie; Yu, Wenwu; Li, Junlei; Yu, Xiaobing; Cao, Fang; Zheng, Guoshuang; Zhang, Yao; Liu, Yu-Peng

doi:10.3892/mmr.2019.10051

Cited by 52 publications

(51 citation statements)

References 59 publications

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“…Consistent with our finding, the PI3K-Akt cascade has long been considered as one of the most significant Smad-independent regulatory route for MSC osteogenesis [52]. For example, Zhang et al has reported that treatment with 1 ng/mL of TGFβ1 augmented the proliferation and mineralization of human hFOB1.19 osteoblasts via the activation of PI3K-Akt [53]. On the other hand, there is also evidence of BMP9-induced enhancement of the PI3K-Akt signaling pathway in an osteo-stimulatory context.…”

Section: Discussionsupporting

confidence: 91%

TGFβ1 induces bone formation from BMP9-activated Bone Mesenchymal Stem Cells, with possible involvement of non-canonical pathways

et al. 2020

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Reconstruction of bone defects is one of the most substantial and difficult clinical challenges in orthopedics. Transforming growth factor beta 1 (TGFβ1) might play an important role in stimulating osteogenic differentiation of bone morphogenetic protein 9 (BMP9)-induced C3H10T1/2 mesenchymal stem cells. In our current study, we examined the potential synergy between TGFβ1 and BMP9 in promoting the osteogenesis of C3H10T1/2 cells, and whether such effects could contribute to bone formation in vivo. Our experiment data indicated that TGFβ1 could increase the expression of osteogenic markers and the formation of mineralized calcium nodules in, while suppressing the proliferation of, BMP9-induced C3H10T1/2 cells. Furthermore, mice intramuscularly injected with BMP9/TGFβ1-transduced C3H10T1/2 cells into the gastrocnemius muscle on their tibiae developed ectopic bone masses with more mature osteoid structures, compared to those grafted with cells expressing BMP9/RFP. Subsequent mechanistic studies found that TGFβ1-induced enhancement of osteogenesis in BMP9-overexpressing C3H10T1/2 cells was accompanied by augmented expression of heat shock protein 47 (HSP47), a collagen-specific molecular chaperone essential for collagen biosynthesis, and can be attenuated by pirfenidone, a known anti-fibrotic inhibitor. Interestingly, protein microarray analysis suggested that TGFβ1/BMP9-dependent osteogenesis of C3H10T1/2 cells seemed to involve several non-canonical signaling pathways such as Janus kinase-signal transducer and activator of transcription, phosphoinositide-3-kinase-protein kinase B, and mitogen-activated protein kinase. These results provided further evidence that TGFβ1 could promote bone formation from BMP9-induced C3H10T1/2 cells and shed important light on the underlying molecular mechanisms.

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Section: Discussionsupporting

confidence: 91%

TGFβ1 induces bone formation from BMP9-activated Bone Mesenchymal Stem Cells, with possible involvement of non-canonical pathways

et al. 2020

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“…Fortunately, novel-miR-3880 and siELF2 could activate PI3K/AKT/mTOR/S6K1 and Bcl2/Bax pathways, and possesses the ability to alleviate the decline of PI3K/AKT/mTOR/S6K1 phosphorylation levels and Bcl2/Bax expression ratio, which might be a reason for the mitigative effects of novel-miR-3880 and siELF2 on reduced MEC proliferation induced by PI3K, AKT, mTOR, or S6K1 inhibitor. It thus appears that the results are consistent with previous research that PI3K/AKT/mTOR/S6K1 pathway activation benefits cell growth (Park et al, 2011;Zhang et al, 2019), and provide sufficient evidence for the participation of novel-miR-3880 and ELF2 in the modulation of PI3K/AKT/mTOR/S6K1 pathway both in vitro and in vivo. In addition, the role of ciRNA13761 and DOCK1 in PI3K/AKT/mTOR/S6K1 pathway and Bcl2/Bax pathway was elaborated, which increases evidence for the regulation of ciRNA13761/novel-miR-3880/ELF2 to PI3K/AKT/mTOR/S6K1 and Bcl2/Bax pathway.…”

Section: Discussionsupporting

confidence: 90%

A Regulatory Circuit Orchestrated by Novel-miR-3880 Modulates Mammary Gland Development

Zhang

Liu

et al. 2020

Front. Cell Dev. Biol.

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Milk casein and triglyceride content are important production traits in goats. Studies on mechanisms in milk casein secretion and mammary gland development is essential for milk goat breeding. miRNAs play an important role in goat lactation. While novel-miR-3880 is highly expressed at goat peak lactation stage, its molecular mechanism has not been studied. The purpose of the present study was to explore the relationship between novel-miR-3880 and lactation, as well as to construct a network among novel-miR-3880, ciRNA13761, and E74 like ETS transcription factor 2 (ELF2), thus further exploring their potential roles in milk components and mammary gland development. ELF2 was previously proven to be important in cell survival and proliferation, and 3-UTR of ELF2 was predicted to have binding sites of novel-miR-3880. Our study found that the overexpression of novel-miR-3880 exerted anti-apoptotic and proliferative roles in GMEC, induced a boost in triglyceride synthesis, and caused a decrease in α s1-, α s2-, and β-casein, but an increase in κ-casein secretion. Furthermore, treatment in mice indicated that novel-miR-3880 could promote mammary gland development and extend the lactation period, while novel-miR-3880 expression was found to be suppressed by ciRNA13761 as a miRNA sponge. The present study explores a mechanism of triglyceride synthesis and casein secretion, and reveals a crosstalk between ciRNA13761/novel-miR-3880/ELF2 axis and PI3K/AKT/mTOR/S6K1 pathway, to gain a better understanding of lactation traits in dairy goats.

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“…Furthermore, previous studies have investigated whether TGF‐β signaling activates PI3K/AKT pathway, either directly or indirectly, in various cell types including osteoblasts, 44 HEK293 cells, 45 prostate cancer cells, 46 and vascular smooth muscle cells 47 . The PI3K/AKT signaling pathway activation has been reported to promote Sertoli cell proliferation.…”

Section: Discussionmentioning

confidence: 99%

miR‐130a promotes immature porcine Sertoli cell growth by activating SMAD5 through the TGF‐β‐PI3K/AKT signaling pathway

et al. 2020

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TGF‑β1 promotes the osteoinduction of human osteoblasts via the PI3K/AKT/mTOR/S6K1 signalling pathway

Cited by 52 publications

References 59 publications

TGFβ1 induces bone formation from BMP9-activated Bone Mesenchymal Stem Cells, with possible involvement of non-canonical pathways

TGFβ1 induces bone formation from BMP9-activated Bone Mesenchymal Stem Cells, with possible involvement of non-canonical pathways

A Regulatory Circuit Orchestrated by Novel-miR-3880 Modulates Mammary Gland Development

miR‐130a promotes immature porcine Sertoli cell growth by activating SMAD5 through the TGF‐β‐PI3K/AKT signaling pathway

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