Activin A Promotes Osteoblastic Differentiation of Human Preosteoblasts through the ALK1-Smad1/5/9 Pathway

Sugii, Hideki; Albougha, Mhd Safwan; Adachi, Orie; Tomita, Hiroka; Tomokiyo, Atsushi; Hasegawa, Daigaku; Yoshida, Shinichiro; Itoyama, Tomohiro; Maeda, Hidefumi

doi:10.3390/ijms222413491

Cited by 3 publications

(2 citation statements)

References 60 publications

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“…Nevertheless, we discovered that bAP15 has an effect on Smad1/5/9. In osteoblasts, activin A induces differentiation from preosteoblasts through the ALK1-Smad1/5/9 pathway downstream of the TGF-β pathway [ 38 ]. However, the role of this pathway in placentation has not been delineated.…”

Section: Discussionmentioning

confidence: 99%

The TGF-β/UCHL5/Smad2 Axis Contributes to the Pathogenesis of Placenta Accreta

Hashimoto,

Miyagawa,

Watanabe

et al. 2023

IJMS

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Placenta accreta is a high-risk condition causing obstetric crisis and hemorrhage; however, its pathogenesis remains unknown. We aimed to identify the factors contributing to trophoblast invasiveness and angiogenic potential, which in turn drive the pathogenesis of placenta accreta. We focused on the transforming growth factor (TGF)-β1-Smad pathway and investigated the intrinsic relationship between the time- and dose-dependent inhibition of the ubiquitinating enzyme UCHL5 using bAP15, a deubiquitinase inhibitor, after TGF-β1 stimulation and the invasive and angiogenic potential of two cell lines, gestational choriocarcinoma cell line JEG-3 and trophoblast cell line HTR-8/SVneo. UCHL5 inhibition negatively regulated TGF-β1-induced Smad2 activation, decreasing extravillous trophoblast invasiveness. Smad1/5/9 and extracellular signal-regulated kinase (ERK) were simultaneously activated, and vascular endothelial growth factor was secreted into the trophoblast medium. However, extravillous trophoblast culture supernatant severely impaired the vasculogenic potential of human umbilical vein endothelial cells. These results suggest that the downstream ERK pathway and Smad1/5/9 potentially regulate the TGF-β1-Smad pathway in extravillous trophoblasts, whereas Smad2 contributes to their invasiveness. The abnormal invasive and angiogenic capacities of extravillous cells, likely driven by the interaction between TGF-β1-Smad and ERK pathways, underlie the pathogenesis of placenta accreta.

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Section: Discussionmentioning

confidence: 99%

The TGF-β/UCHL5/Smad2 Axis Contributes to the Pathogenesis of Placenta Accreta

Hashimoto,

Miyagawa,

Watanabe

et al. 2023

IJMS

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“…Our recent study revealed that calcium supplementation can induce the osteoblastic differentiation and mineralization of HPDLSCs [ 56 ] and Saos2 cells [ 57 ]. Thus, we used CaCl 2 for the induction of osteoblastic differentiation of these cells.…”

Section: Methodsmentioning

confidence: 99%

Decorin Promotes Osteoblastic Differentiation of Human Periodontal Ligament Stem Cells

et al. 2022

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The aim of this study is to clarify the biological functions of decorin (DCN) in the healing and regeneration of wounded periodontal tissue. We investigated the expression pattern of DCN during the healing of wounded periodontal tissue in rats by immunohistochemistry and the effects of DCN on the osteoblastic differentiation of human periodontal ligament (PDL) stem cells (HPDLSCs) and preosteoblasts by Alizarin red S staining, quantitative reverse transcription-polymerase chain reactions, and western blotting. The expression of DCN was increased around the wounded PDL tissue on day 5 after surgery compared with the nonwounded PDL tissue, whereas its expression was not changed in the osteoblastic layer around the wounded alveolar bone. Furthermore, DCN promoted the osteoblastic differentiation of HPDLSCs, but it did not affect the osteoblastic differentiation of preosteoblasts. ERK1/2 phosphorylation was upregulated during the DCN-induced osteoblastic differentiation of HPDLSCs. DCN did not affect proliferation, migration, or the PDL-related gene expression of HPDLSCs. In conclusion, this study demonstrates that DCN has a role in the healing of wounded periodontal tissue. Furthermore, DCN secreted from PDL cells may contribute to bone healing by upregulating osteoblastic differentiation through ERK1/2 signaling in HPDLSCs, indicating a therapeutic effect of DCN in periodontal tissue regeneration.

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Exosomes from Human Periodontal Ligament Stem Cells Promote Differentiation of Osteoblast-like Cells and Bone Healing in Rat Calvarial Bone

Albougha,

Sugii,

Adachi

et al. 2024

Biomolecules

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Deep caries and severe periodontitis cause bone resorption in periodontal tissue, and severe bone resorption leads to tooth loss. Periodontal ligament stem cells (PDLSCs) are important for the healing of defective periodontal tissue. It is increasingly understood that healing of periodontal tissue is mediated through the secretion of trophic factors, particularly exosomes. This study investigated the effects of exosomes from human PDLSCs (HPDLSCs-Exo) on human osteoblast-like cells in vitro and on the healing of rat calvarial bone defects in vivo. HPDLSCs-Exo were isolated and characterized by their particle shape, size (133 ± 6.4 nm), and expression of surface markers (CD9, CD63, and CD81). In vitro results showed that HPDLSCs-Exo promoted the migration, mineralization, and expression of bone-related genes such as alkaline phosphatase (ALP), bone morphogenetic protein 2 (BMP2), osteocalcin (OCN), and osteopontin (OPN) in human osteoblast-like cells. Furthermore, in vivo results showed that more newly formed bone was observed in the HPDLSCs-Exo-treated group than in the non-treated group at the defect sites in rats. These results indicated that HPDLSCs-Exo could promote osteogenesis in vitro and in vivo, and this suggests that HPDLSCs-Exo may be an attractive treatment tool for bone healing in defective periodontal tissue.

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Activin A Promotes Osteoblastic Differentiation of Human Preosteoblasts through the ALK1-Smad1/5/9 Pathway

Cited by 3 publications

References 60 publications

The TGF-β/UCHL5/Smad2 Axis Contributes to the Pathogenesis of Placenta Accreta

The TGF-β/UCHL5/Smad2 Axis Contributes to the Pathogenesis of Placenta Accreta

Decorin Promotes Osteoblastic Differentiation of Human Periodontal Ligament Stem Cells

Exosomes from Human Periodontal Ligament Stem Cells Promote Differentiation of Osteoblast-like Cells and Bone Healing in Rat Calvarial Bone

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