Inhibiting PPARγ by erythropoietin while upregulating TAZ by IGF1 synergistically promote osteogenic differentiation of mesenchymal stem cells

Zhou, Jianwei; Wei, Fulan; Ma, Yuetao

doi:10.1016/j.bbrc.2016.07.049

Cited by 15 publications

(13 citation statements)

References 23 publications

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“…As reported, TAZ binds strongly to the Pro‐Pro‐ X‐Tyr motif found within regulatory regions of RUNX2 and PPARγ . It interacted with RUNX2 and co‐activates RUNX2‐dependent gene transcription, while interacting with PPARγ and repressing its downstream target gene expression . Consistently, our results suggested that Sal B at least partially targeted TAZ to regulate the cells differentiation into osteoblasts or adipocytes.…”

Section: Discussionsupporting

confidence: 89%

“…TAZ, a transcriptional modulator, could interact with kinds of transcription factors to influence the stem cells fate determination . As reported, TAZ binds strongly to the Pro‐Pro‐ X‐Tyr motif found within regulatory regions of RUNX2 and PPARγ . It interacted with RUNX2 and co‐activates RUNX2‐dependent gene transcription, while interacting with PPARγ and repressing its downstream target gene expression .…”

Section: Discussionmentioning

confidence: 86%

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Sal B targets TAZ to facilitate osteogenesis and reduce adipogenesis through MEK‐ERK pathway

Wang

et al. 2019

J Cellular Molecular Medi

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Salvianolic acid B (Sal B), a major bioactive component of Chinese herb, was identified as a mediator for bone metabolism recently. The aim of this study is to investigate the underlying mechanisms by which Sal B regulates osteogenesis and adipogenesis. We used MC3T3‐E1 and 3T3‐L1 as the study model to explore the changes of cell differentiation induced by Sal B. The results indicated that Sal B at different concentrations had no obvious toxicity effects on cell proliferation during differentiation. Furthermore, Sal B facilitated osteogenesis but inhibited adipogenesis by increasing the expression of transcriptional co‐activator with PDZ‐binding motif (TAZ). Accordingly, TAZ knock‐down offset the effects of Sal B on cell differentiation into osteoblasts or adipocytes. Notably, the Sal B induced up‐expression of TAZ was blocked by U0126 (the MEK‐ERK inhibitor), rather than LY294002 (the PI3K‐Akt inhibitor). Moreover, Sal B increased the p‐ERK/ERK ratio to regulate the TAZ expression as well as the cell differentiation. In summary, this study suggests for the first time that Sal B targets TAZ to facilitate osteogenesis and reduce adipogenesis by activating MEK‐ERK signalling pathway, which provides evidence for Sal B to be used as a potential therapeutic agent for the management of bone diseases.

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Section: Discussionsupporting

confidence: 89%

Section: Discussionmentioning

confidence: 86%

Sal B targets TAZ to facilitate osteogenesis and reduce adipogenesis through MEK‐ERK pathway

Wang

et al. 2019

J Cellular Molecular Medi

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“…Given insulin/IGF-I's role in mesenchymal stem cell (MSC) osteogenesis [22,23,[28][29][30], we hypothesized that insulin promotes proliferation and in vitro osteogenic differentiation of TPCs. Our results indicate that insulin significantly increased TPC proliferation after 3 days of monolayer culture.…”

Section: Discussionmentioning

confidence: 99%

Insulin Enhances the In Vitro Osteogenic Capacity of Flexor Tendon-Derived Progenitor Cells

Durgam

Altmann

Coughlin

et al. 2019

Stem Cells International

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There is increased incidence of tendon disorders and decreased tendon healing capacity in people with diabetes mellitus (DM). Recent studies have also suggested pathological ossification in repair tendon of people with DM. Therefore, the objective of this study is to investigate the effects of insulin supplementation, an important pathophysiologic stimulus of DM, on tendon progenitor cell (TPC) proliferation and in vitro osteogenic capacity. Passage 3 TPCs were isolated from collagenase-digested, equine superficial digital flexor tendons. TPC proliferation was measured via MTT assay after 3 days of monolayer culture in medium supplemented with 0, 0.007, 0.07, and 0.7 nM insulin. In vitro osteogenic capacity of TPCs (Alizarin Red staining, osteogenic mRNA expression, and alkaline phosphatase bioactivity) was assessed with 0, 0.07, and 0.7 nM insulin-supplemented osteogenic induction medium. Insulin (0.7 nM) significantly increased TPC proliferation after 3 days of monolayer culture. Alizarin Red staining of insulin-treated TPC osteogenic cultures demonstrated robust cell aggregation and mineralized matrix secretion, in a dose-dependent manner. Runx2, alkaline phosphatase, and Osteonectin mRNA and alkaline phosphatase bioactivity of insulin-treated TPC cultures were significantly higher at day 14 of osteogenesis compared to untreated controls. Addition of picropodophyllin (PPP), a selective IGF-I receptor inhibitor, mitigated the increased osteogenic capacity of TPCs, indicating that IGF-I signaling plays an important role. Our findings indicate that hyperinsulinemia may alter TPC phenotype and subsequently impact the quality of repair tendon tissue.

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“…Using SEM, we showed that cells in the scaffold attached around the pores, and we highlighted the good morphology and viability of BMMSCs grown under these conditions. Finally, we used ALP-a commonly assessed marker of osteogenesis-to confirm the osteogenic potential of BMMSCs on the scaffolds 29) . We found significantly elevated ALP activity in cells growing on the BMP-6-containing CCM scaffolds.…”

Section: Discussionmentioning

confidence: 99%

Characterization of a Porous BMP-6-Loaded Composite Scaffold for Bone Regeneration in Rat Calvarial Bone Defects

Zhang

Yang

et al. 2019

J. Hard Tissue Biology.

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Biocompatible scaffolding materials play an important role in bone tissue engineering. This study sought to assess the biocompatibility and osteoinductivity of a chitosan (CS)/collagenⅠ(ColI)/multi-walled carbon nanotube (MWCNT) composite scaffold blended with bone morphogenetic protein-6 (BMP-6) and seeded with bone marrow mesenchymal stem cells (BMMSCs). The composite was fabricated using varying quantities of MWCNT to determine the appropriate combination, and combined with BMP-6 by blending and vacuum freeze-drying. Scanning electron microscopy (SEM) was used to observe the morphology of the CS/ColI/MWCNT (CCM) scaffolds. The porosity and mechanical properties of the composite scaffolds were measured. Scaffolds were seeded with BMMSCs in vitro and analyzed using SEM, CCK-8 assay and alkaline phosphatase (ALP) activity. To assess the in vivo utility of the composite scaffolds, critical-sized calvarial bone defects were prepared in 15 Sprague-Dawley rats and implanted with pre-seeded scaffolds (the CCM scaffold+BMMSCs group and the BMP-6/CCM scaffold+BMMSCs group) or left untreated (control). Three-dimensional computerized tomography and hematoxylin-eosin (HE) staining were used to evaluate bone formation at 8 weeks postoperatively. We found that higher concentrations of MWCNT decreased the porosity of the scaffold but increased its mechanical strength. In vitro, we found that BMP-6/CCM scaffolds provided the best conditions for BMMSCs proliferation and osteogenic differentiation. Similarly, BMP-6/CCM scaffolds seeded with BMMSCs could more effectively induce new bone formation in critical-sized calvarial bone defects compared with the other three groups. The BMP-6/CCM scaffold possesses good biocompatibility and induces bone formation in vitro and in vivo.

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Inhibiting PPARγ by erythropoietin while upregulating TAZ by IGF1 synergistically promote osteogenic differentiation of mesenchymal stem cells

Cited by 15 publications

References 23 publications

Sal B targets TAZ to facilitate osteogenesis and reduce adipogenesis through MEK‐ERK pathway

Sal B targets TAZ to facilitate osteogenesis and reduce adipogenesis through MEK‐ERK pathway

Insulin Enhances the In Vitro Osteogenic Capacity of Flexor Tendon-Derived Progenitor Cells

Characterization of a Porous BMP-6-Loaded Composite Scaffold for Bone Regeneration in Rat Calvarial Bone Defects

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