Smad7 inhibits differentiation and mineralization of mouse osteoblastic cells

Yano, Masato; Inoue, Yasuhiro; Tobimatsu, Takako; Hendy, Geoffrey N.; Canaff, Lucie; Sugimoto, Toshitsugu; Seino, Susumu; Kaji, Hiroshi

doi:10.1507/endocrj.ej12-0022

Cited by 41 publications

(38 citation statements)

References 27 publications

(36 reference statements)

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“…BMP7 signaling is regulated by I-Smads (including Smad6 and Smad7). In fact, I-Smads inhibit BMP rather than TGF-β signaling [33]. High levels of gremlin1 may block BMP-7 activity through upregulation of Smad6 expression, since its overexpression in HSCs promoted Smad6, but not Smad7 expression in the current study.…”

Section: Discussionmentioning

confidence: 62%

Suppression of hepatic stellate cell activation through downregulation of gremlin1 expression by the miR-23b/27b cluster

Zeng

Zhang

et al. 2016

Oncotarget

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The imbalance between transforming growth factor β and bone morphogenetic protein 7 signaling pathways is a critical step in promoting hepatic stellate cell activation during hepatic fibrogenesis. Gremlin1 may impair the balance. Something remains unclear about the regulatory mechanisms of gremlin1 action on hepatic stellate cell activation and hepatic fibrosis. In the current study, gremlin1 overexpression promotes activation of hepatic stellate cells. Knockdown of gremlin1 with siRNAs suppresses hepatic stellate cell activation and attenuates hepatic fibrosis in rat model. Our results also show that miR-23b/27b cluster members bind to 3′-untranslated region of gremlin1 resulting in reduction of transforming growth factor β, α-smooth muscle actin and collagenI α1/2 gene expression. Our findings suggest that gremlin1 promotes hepatic stellate cell activation and hepatic fibrogenesis through impairment of the balance between transforming growth factor β and bone morphogenetic protein 7 signaling pathways. The miR-23b/27b cluster suppresses activation of hepatic stellate cells through binding gremlin1 to rectify the imbalance.

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Section: Discussionmentioning

confidence: 62%

Suppression of hepatic stellate cell activation through downregulation of gremlin1 expression by the miR-23b/27b cluster

Zeng

Zhang

et al. 2016

Oncotarget

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“…As expected, the negative correlation between miR-17-5p and SMAD7 in ON tissues of 20 patients was proven (Figure 2e, R 2 =0.5440, P <0.001). Furthermore, it has been reported that SMAD7 might act as a suppressor of bone formation, 19 so we examined the enrichment of SMAD7 during osteoblast differentiation. Interestingly, SMAD7 expression was steadily downregulated during bone formation after administration of BMP-2, which was the opposite of the expression pattern of miR-17-5p (Figure 2f).…”

Section: Resultsmentioning

confidence: 99%

MiR-17-5p modulates osteoblastic differentiation and cell proliferation by targeting SMAD7 in non-traumatic osteonecrosis

Jia

Feng

et al. 2014

Exp Mol Med

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MicroRNAs (miRNAs) have recently been recognized to have a role in human orthopedic disorders. The objective of our study was to explore the expression profile and biological function of miRNA-17-5p (miR-17-5p), which is well known to be related to cancer cell proliferation and invasion, in osteoblastic differentiation and in cell proliferation. The expression levels of miR-17-5p in the femoral head mesenchymal stem cells of 20 patients with non-traumatic osteonecrosis (ON) and 10 patients with osteoarthritis (OA) were examined by quantitative reverse transcription-PCR (qRT–PCR). Furthermore, the interaction between miR-17-5p and SMAD7 was observed. We found that in non-traumatic ON samples the level of mature miR-17-5p was significantly lower than that of OA samples (P=0.0002). By targeting SMAD7, miR-17-5p promoted nuclear translocation of β-catenin, enhanced expression of COL1A1 and finally facilitated the proliferation and differentiation of HMSC-bm cells. We also demonstrated that restoring expression of SMAD7 in HMSC-bm cells partially reversed the function of miR-17-5p. Together, our data suggested a theory that dysfunction of a network containing miR-17-5p, SMAD7 and β-catenin could contribute to ON pathogenesis. The present study prompts the potential clinical value of miR-17-5p in non-traumatic ON.

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“…While Smad7 inhibits TGF- β /BMP signaling, Smad6 is less effective in inhibiting TGF- β signaling. It has been reported that Smad7 can inhibit ALP activity and suppress type I collagen mRNA and protein levels [46]. MicroRNA 21 has been shown to be a key regulator of TGF- β signaling [47] and Smad7 was found to be one of its target genes [21, 40, 43].…”

Section: Discussionmentioning

confidence: 99%

Pulsed Electromagnetic Field Regulates MicroRNA 21 Expression to Activate TGF-β Signaling in Human Bone Marrow Stromal Cells to Enhance Osteoblast Differentiation

Selvamurugan

Rifkin

et al. 2017

Stem Cells International

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Pulsed electromagnetic fields (PEMFs) have been documented to promote bone fracture healing in nonunions and increase lumbar spinal fusion rates. However, the molecular mechanisms by which PEMF stimulates differentiation of human bone marrow stromal cells (hBMSCs) into osteoblasts are not well understood. In this study the PEMF effects on hBMSCs were studied by microarray analysis. PEMF stimulation of hBMSCs' cell numbers mainly affected genes of cell cycle regulation, cell structure, and growth receptors or kinase pathways. In the differentiation and mineralization stages, PEMF regulated preosteoblast gene expression and notably, the transforming growth factor-beta (TGF-β) signaling pathway and microRNA 21 (miR21) were most highly regulated. PEMF stimulated activation of Smad2 and miR21-5p expression in differentiated osteoblasts, and TGF-β signaling was essential for PEMF stimulation of alkaline phosphatase mRNA expression. Smad7, an antagonist of the TGF-β signaling pathway, was found to be miR21-5p's putative target gene and PEMF caused a decrease in Smad7 expression. Expression of Runx2 was increased by PEMF treatment and the miR21-5p inhibitor prevented the PEMF stimulation of Runx2 expression in differentiating cells. Thus, PEMF could mediate its effects on bone metabolism by activation of the TGF-β signaling pathway and stimulation of expression of miR21-5p in hBMSCs.

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Smad7 inhibits differentiation and mineralization of mouse osteoblastic cells

Cited by 41 publications

References 27 publications

Suppression of hepatic stellate cell activation through downregulation of gremlin1 expression by the miR-23b/27b cluster

Suppression of hepatic stellate cell activation through downregulation of gremlin1 expression by the miR-23b/27b cluster

MiR-17-5p modulates osteoblastic differentiation and cell proliferation by targeting SMAD7 in non-traumatic osteonecrosis

Pulsed Electromagnetic Field Regulates MicroRNA 21 Expression to Activate TGF-β Signaling in Human Bone Marrow Stromal Cells to Enhance Osteoblast Differentiation

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