ArticlePloS one2016
Leptin and Pro-Inflammatory Stimuli Synergistically Upregulate MMP-1 and MMP-3 Secretion in Human Gingival Fibroblasts.
Article in PloS one, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers, 1 of them a synthesis that pooled it.
What it found
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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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
19 citing papers in PubMed, 1 synthesis or guideline pooled it, 29 citations in OpenAlex.
- Association of circulating leptin and adiponectin with periodontitis: a systematic review and meta-analysis.BMC oral health · 2017Pooled it
- Trial
- Association of Gingival Crevicular Fluid Leptin Levels With Stages of Periodontitis: A Cross-Sectional Study.International dental journal · 2026Article
- Periodontal disease and endocrine imbalance: a molecular pathways perspective.Frontiers in dental medicine · 2026Review
- Salivary Biomarker Profile in Periodontal Diseases: A Cross-Sectional Study on Leptin, Adiponectin, and Calprotectin.Diagnostics (Basel, Switzerland) · 2025Article
- Article
- MMP3 at the crossroads: Linking molecular pathways to disease diagnosis and therapy.Pharmacological research · 2025Review
- Article
- Disparity in the Influence of Implant Provisional Materials on Human Gingival Fibroblasts with Different Phases of Cell Settlement: An In Vitro Study.International journal of molecular sciences · 2023Article
- The Emerging Role of MMP12 in the Oral Environment.International journal of molecular sciences · 2023Review
- Review
- Leptin Accelerates Endothelial Wound Healing: Role of Endothelial Nitric Oxide Synthase Expression.Anatolian journal of cardiology · 2022Article
- Current knowledge of leptin in wound healing: A collaborative review.Frontiers in pharmacology · 2022Review
- Photobiomodulation of oral fibroblasts stimulated with periodontal pathogens.Lasers in medical science · 2021Article
- Targeting hepatocyte growth factor in epithelial-stromal interactions in an in vitro experimental model of human periodontitis.Odontology · 2021Article
- Leptin reduces in vitro cementoblast mineralization and survival as well as induces PGE2 release by ERK1/2 commitment.Clinical oral investigations · 2021Article
- Palmatine as an Agent Against Metabolic Syndrome and Its Related Complications: A Review.Drug design, development and therapy · 2020Review
- Leptin-induced signaling pathways in cancer cell migration and invasion.Cellular oncology (Dordrecht, Netherlands) · 2019Review
- NAMPT enzyme activity regulates catabolic gene expression in gingival fibroblasts during periodontitis.Experimental & molecular medicine · 2017Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
introductionGingival fibroblast-mediated extracellular matrix remodelling is implicated in the pathogenesis of periodontitis, yet the stimuli that regulate this response are not fully understood. The immunoregulatory adipokine leptin is detectable in the gingiva, human gingival fibroblasts express functional leptin receptor mRNA and leptin is known to regulate extracellular matrix remodelling responses in cardiac fibroblasts. We therefore hypothesised that leptin would enhance matrix metalloproteinase secretion in human gingival fibroblasts. METHODS AND
resultsWe used in vitro cell culture to investigate leptin signalling and the effect of leptin on mRNA and protein expression in human gingival fibroblasts. We confirmed human gingival fibroblasts expressed cell surface leptin receptor, found leptin increased matrix metalloproteinase-1, -3, -8 and -14 expression in human gingival fibroblasts compared to unstimulated cells, and observed that leptin stimulation activated MAPK, STAT1/3 and Akt signalling in human gingival fibroblasts. Furthermore, leptin synergised with IL-1 or the TLR2 agonist pam2CSK4 to markedly enhance matrix metalloproteinase-1 and -3 production by human gingival fibroblasts. Signalling pathway inhibition demonstrated ERK was required for leptin-stimulated matrix metalloproteinase-1 expression in human gingival fibroblasts; whilst ERK, JNK, p38 and STAT3 were required for leptin+IL-1- and leptin+pam2CSK4-induced matrix metalloproteinase-1 expression. A genome-wide expression array and gene ontology analysis confirmed genes differentially expressed in leptin+IL-1-stimulated human gingival fibroblasts (compared to unstimulated cells) were enriched for extracellular matrix organisation and disassembly, and revealed that matrix metalloproteinase-8 and -12 were also synergistically upregulated by leptin+IL-1 in human gingival fibroblasts.
conclusionsWe conclude that leptin selectively enhances the expression and secretion of certain matrix metalloproteinases in human gingival fibroblasts, and suggest that gingival fibroblasts may have an ECM-degrading phenotype during conditions of hyperleptinaemia (e.g., obesity, type 2 diabetes mellitus, exogenous leptin therapy).
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