ArticleJournal of dental research2017
Differential Expression and Roles of Secreted Frizzled-Related Protein 5 and the Wingless Homolog Wnt5a in Periodontitis.
Article in Journal of dental research, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
21 citing papers in PubMed, 1 synthesis or guideline pooled it, 43 citations in OpenAlex.
- Research Progress on Anti-Inflammatory Adipokine SFRP5-Mediated Lipid Metabolism and Its Potential Role in Neural Development.Immunity, inflammation and disease · 2026Pooled it
- Periodontitis as a Model for Inflammatory Uncoupling of Bone Remodeling.Journal of periodontal research · 2026Review
- Wnt/β-Catenin Pathway and Hydraulic Calcium Silicate-Based Cements: A Narrative Review.Dentistry journal · 2026Review
- Single-cell spatial atlas of smoking-induced changes in human gingival tissues.International journal of oral science · 2025Article
- Different effects of abnormal mechanical stress on temporomandibular joint cartilage, subchondral bone, and discs.Frontiers in physiology · 2025Review
- Three-Dimensional Organotypic Systems for Modelling and Understanding Molecular Regulation of Oral Dentogingival Tissues.International journal of molecular sciences · 2024Review
- Wnt signaling in periodontitis.Clinical oral investigations · 2023Article
- Complement Is Required for Microbe-Driven Induction of Th17 and Periodontitis.Journal of immunology (Baltimore, Md. : 1950) · 2022Article
- Anti-Inflammatory Effects of (3Pharmaceuticals (Basel, Switzerland) · 2022Article
- SFRP5 inhibits melanin synthesis of melanocytes in vitiligo by suppressing the Wnt/β-catenin signaling.Genes & diseases · 2021Article
- Application of Ligature-Induced Periodontitis in Mice to Explore the Molecular Mechanism of Periodontal Disease.International journal of molecular sciences · 2021Review
- Role of Wnt5a in periodontal tissue development, maintenance, and periodontitis: Implications for periodontal regeneration (Review).Molecular medicine reports · 2021Review
- Exosomes from TNF-α-treated human gingiva-derived MSCs enhance M2 macrophage polarization and inhibit periodontal bone loss.Acta biomaterialia · 2021Article
- An Overview of Potential Therapeutic Agents Targeting WNT/PCP Signaling.Handbook of experimental pharmacology · 2021Review
- Deep Learning Reveals Key Immunosuppression Genes and Distinct Immunotypes in Periodontitis.Frontiers in genetics · 2021Article
- Oral Osteomicrobiology: The Role of Oral Microbiota in Alveolar Bone Homeostasis.Frontiers in cellular and infection microbiology · 2021Review
- Current understanding of periodontal disease pathogenesis and targets for host-modulation therapy.Periodontology 2000 · 2020Review
- Erythromycin inhibits neutrophilic inflammation and mucosal disease by upregulating DEL-1.JCI insight · 2020Article
- Sfrp5/Wnt Pathway: A Protective Regulatory System in Atherosclerotic Cardiovascular Disease.Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research · 2019Review
- The Wnt antagonist and secreted frizzled-related protein 5: implications on lipid metabolism, inflammation, and type 2 diabetes mellitus.Bioscience reports · 2018Review
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 3 countries.
Funding
Abstract
The Wingless/integrase-1 (Wnt) family of protein ligands and their functional antagonists, secreted frizzled-related proteins (sFRPs), regulate various biological processes ranging from embryonic development to immunity and inflammation. Wnt5a and sFRP5 comprise a typical ligand/antagonist pair, and the former molecule was recently detected at the messenger RNA (mRNA) level in human periodontitis. The main objective of this study was to investigate the interrelationship of expression of Wnt5a and sFRP5 in human periodontitis (as compared to health) and to determine their roles in inflammation and bone loss in an animal model. We detected both Wnt5a and sFRP5 mRNA in human gingiva, with Wnt5a dominating in diseased and sFRP5 in healthy tissue. Wnt5a and sFRP5 protein colocalized in the gingival epithelium, suggesting epithelial cell expression, which was confirmed in cultured human gingival epithelial cells (HGECs). The HGEC expression of Wnt5a and sFRP5 was differentially regulated by a proinflammatory stimulus (lipopolysaccharide [LPS] from Porphyromonas gingivalis) in a manner consistent with the clinical observations (i.e., LPS upregulated Wnt5a and downregulated sFRP5). In HGECs, exogenously added Wnt5a enhanced whereas sFRP5 inhibited LPS-induced inflammation, as monitored by interleukin 8 production. Consistent with this, local treatment with sFRP5 in mice subjected to ligature-induced periodontitis inhibited inflammation and bone loss, correlating with decreased numbers of osteoclasts in bone tissue sections. As in humans, mouse periodontitis was associated with high expression of Wnt5a and low expression of sFRP5, although this profile was reversed after treatment with sFRP5. In conclusion, we demonstrated a novel reciprocal relationship between sFRP5 and Wnt5a expression in periodontal health and disease, paving the way to clinical investigation of the possibility of using the Wnt5a/sFRP5 ratio as a periodontitis biomarker. Moreover, we showed that sFRP5 blocks experimental periodontal inflammation and bone loss, suggesting a promising platform for the development of a new host modulation therapy in periodontitis.
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Registered trials
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