ArticleCell death & disease2018
Bone morphogenetic protein 2 promotes human trophoblast cell invasion by upregulating N-cadherin via non-canonical SMAD2/3 signaling.
Article in Cell death & disease, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 74 citations in OpenAlex.
- Sperm AluY Epimutations in Male Partners of Couples with Unexplained Recurrent Pregnancy Loss.bioRxiv : the preprint server for biology · 2026Article
- Taxifolin Inhibits Invasion and Endovascular Differentiation of Extravillous Trophoblast HTR-8/SVneo Cells.Cells · 2026Article
- Deciphering the maternal uterine signals that shape placenta development.Reproduction (Cambridge, England) · 2026Review
- BMP6 as a therapeutic target for preeclampsia: enhancing trophoblast invasion and vascular mimicry.Cellular and molecular life sciences : CMLS · 2026Article
- Beyond traditional models: microfluidic technologies for engineering the human placentaFrontiers in bioengineering and biotechnology · 2026Review
- The BMP Signaling Pathway: Bridging Maternal-Fetal Crosstalk in Early Pregnancy.Reproductive sciences (Thousand Oaks, Calif.) · 2025Review
- Bone morphogenetic protein-4 induced matrix turnover and osteogenic differentiation-related molecules of stem cells from apical papilla and its associated ALK/Smad signaling.Journal of dental sciences · 2025Article
- Cross-Species Insights into Trophoblast Invasion During Placentation Governed by Immune-Featured Trophoblast Cells.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Unraveling the Dynamics of Estrogen and Progesterone Signaling in the Endometrium: An Overview.Cells · 2024Review
- TGFβ signalling: a nexus between inflammation, placental health and preeclampsia throughout pregnancy.Human reproduction update · 2024Review
- Unraveling the molecular mechanisms driving enhanced invasion capability of extravillous trophoblast cells: a comprehensive review.Journal of assisted reproduction and genetics · 2024Review
- Fibronectin mediates activin A-promoted human trophoblast migration and acquisition of endothelial-like phenotype.Cell communication and signaling : CCS · 2024Article
- Placental microRNAs relate to early childhood growth trajectories.Pediatric research · 2023Article
- Establishment of the fetal-maternal interface: developmental events in human implantation and placentation.Frontiers in cell and developmental biology · 2023Review
- ID3 mediates BMP2-induced downregulation of ICAM1 expression in human endometiral stromal cells and decidual cells.Frontiers in cell and developmental biology · 2023Article
- An miRNA-mRNA integrative analysis in human placentas and mice: role of the Smad2/miR-155-5p axis in the development of fetal growth restriction.Frontiers in bioengineering and biotechnology · 2023Article
- Differential bioactivity of four BMP-family members as function of biomaterial stiffness.Biomaterials · 2022Article
- Bone morphogenetic protein 2 inhibits growth differentiation factor 8-induced cell signaling via upregulation of gremlin2 expression in human granulosa-lutein cells.Reproductive biology and endocrinology : RB&E · 2021Article
- MicroRNA-378a-3p is overexpressed in psoriasis and modulates cell cycle arrest in keratinocytes via targeting BMP2 gene.Scientific reports · 2021Article
- INO80 participates in the pathogenesis of recurrent miscarriage by epigenetically regulating trophoblast migration and invasion.Journal of cellular and molecular medicine · 2021Article
Corrections and comments
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Authors and funding
6 authors at 4 institutions in 2 countries.
Funding
Abstract
BMP2 expression is spatiotemporally correlated with embryo implantation and is crucial for endometrial decidualization and fertility in mice. BMP2 has been reported to increase the mesenchymal adhesion molecule N-cadherin and enhance cell invasion in cancer cells; moreover, studies suggest that N-cadherin promotes placental trophoblast invasion. However, whether BMP2 can promote trophoblast cell invasion during placentation remains unknown. The objective of our study was to investigate the effects of BMP2 on human trophoblast cell invasion and the involvement of N-cadherin and SMAD signaling. Primary and immortalized (HTR8/SVneo) cultures of human extravillous trophoblast (EVT) cells were used as study models. Treatment with recombinant human BMP2 increased HTR8/SVneo cell transwell Matrigel invasion as well as N-cadherin mRNA and protein levels, but had no significant effect on cell proliferation. Likewise, BMP2 treatment enhanced primary human EVT cell invasion and N-cadherin production. Basal and BMP2-induced invasion were attenuated by small interfering RNA-mediated downregulation of N-cadherin in both HTR8/SVneo and primary EVT cells. Intriguingly, BMP2 induced the phosphorylation/activation of both canonical SMAD1/5/8 and non-canonical SMAD2/3 signaling in HTR8/SVneo and primary EVT cells. Knockdown of SMAD2/3 or common SMAD4 totally abolished the effects of BMP2 on N-cadherin upregulation in HTR8/SVneo cells. Upregulation of SMAD2/3 phosphorylation and N-cadherin were totally abolished by type I receptor activin receptor-like kinases 2/3 (ALK2/3) inhibitor DMH1; moreover, knockdown of ALK2 or ALK3 inhibited N-cadherin upregulation. Interestingly, activation of SMAD2/3 and upregulation of N-cadherin were partially attenuated by ALK4/5/7 inhibitor SB431542 or knockdown of ALK4, but not ALK5. Our results show that BMP2 promotes trophoblast cell invasion by upregulating N-cadherin via non-canonical ALK2/3/4-SMAD2/3-SMAD4 signaling.
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