ArticleDrug design, development and therapy2022
Noncanonical Wnt5a Signaling Suppresses Hippo/TAZ-Mediated Osteogenesis Partly Through the Canonical Wnt Pathway in SCAPs.
Article in Drug design, development and therapy, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed, 7 citations in OpenAlex.
- New insights into bone pathology through a transcriptomic profiling of an osteoblast model of Gaucher disease.Molecular genetics and metabolism reports · 2026Article
- Sfrp4 Is Required for Proper Dental Formation and Stem Cell Regulation.Journal of dental research · 2026Article
- Regional diversity of cranial skeletal stem cells governs bone morphogenetic protein-2 mediated bone regeneration.Nature communications · 2026Article
- Article
- Optineurin Cooperates With NRF2 to Regulate Tooth Root Morphogenesis by Controlling Mitochondrial Dynamics and Apoptosis.Cell proliferation · 2025Article
- The canonical Wnt pathway in osteoporosis: a scoping review of key compounds and proteins modulating Wnt-induced osteogenesis.Frontiers in pharmacology · 2025Review
- Emerging Roles of YAP/TAZ in Tooth and Surrounding: from Development to Regeneration.Stem cell reviews and reports · 2023Review
- Stem Cells from the Apical Papilla (SCAPs): Past, Present, Prospects, and Challenges.Biomedicines · 2023Review
- Notoginsenoside R1 Promotes Proliferation and Osteogenic Differentiation of hPDLSCs via Wnt/β-Catenin Signaling Pathway.Drug design, development and therapy · 2022Article
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Authors and funding
7 authors at 3 institutions in 1 country.
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No grant is acknowledged in the PubMed record.
Abstract
purposeStem cells from the apical papilla (SCAPs) are promising seed cells for tissue regeneration medicine and possess the osteogenic differentiation potential. Wnt5a, a typical ligand of the noncanonical Wnt pathway, exhibits diverse roles in the regulation of osteogenesis. The transcriptional co-activator with PDZ-binding motif (TAZ, WWTR1) is a core regulator in the Hippo pathway and regulates stem behavior including osteogenic differentiation. This study aims to examine how Wnt5a regulates SCAPs osteogenesis and explore the precise mechanistic relationship between Wnt5a and TAZ.
methodsSCAPs were isolated from developing apical papilla tissue of extracted human immature third molars in vitro. ALP staining, ALP activity and Alizarin red staining were used to evaluate osteogenic capacity. Osteogenic-related factors were assessed by qRT-PCR or Western blotting. Additionally, the receptor tyrosine kinase-like orphan receptor 2 (ROR2) was detected by immunocytofluorescence staining and silenced by small interfering RNA to verify the function of Wnt5a/ROR2 in TAZ-mediated osteogenesis. And we constructed TAZ-overexpression and β-catenin-overexpression SCAPs generated by lentivirus to explore the precise mechanistic relationship between Wnt5a and TAZ.
resultsWnt5a (100ng/mL) significantly suppressed ALP activity, mineralization nodules formation, expression of osteogenic-related factors. Meanwhile, it decreased the expression of TAZ mRNA and protein. TAZ overexpression promoted osteogenesis of SCAPs while Wnt5a could block TAZ-mediated osteogenesis. Furthermore, ROR2 siRNA (siROR2) was found to upregulate TAZ and canonical Wnt pathway signaling related molecules such as β-catenin, GSK3β and p-GSK3β. The suppression of Wnt5a/ROR2 on osteogenesis was significantly reversed by β-catenin overexpression through Wnt5a/ROR2/β-catenin/TAZ pathway.
conclusionTaken together, the present study demonstrates that Wnt5a suppresses TAZ-mediated osteogenesis of SCAPs and there may be a Wnt5a/ROR2/β-catenin/TAZ pathway regulating osteogenesis of SCAPs. Moreover, Wnt5a could be a candidate for regulators in tissue regeneration.
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