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Review Open Access

Klotho in periodontitis: Mechanisms, biomarker potential and therapeutic implications (Review)

  • Authors:
    • Gauri Vilas Patil
    • Jaideep Mahendra
    • Deepa Ponnaiyan
  • View Affiliations / Copyright

    Affiliations: Department of Periodontics, Meenakshi Ammal Dental College and Hospital, Meenakshi Academy of Higher Education and Research, Chennai, Tamil Nadu 600069, India, Department of Periodontics, Sri Ramaswamy Memorial Dental College Ramapuram, Chennai, Tamil Nadu 600089, India
    Copyright: © Patil et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY 4.0].
  • Article Number: 79
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    Published online on: July 14, 2026
       https://doi.org/10.3892/wasj.2026.494
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Abstract

Periodontitis is a chronic inflammatory disease characterized by the destruction of tooth‑ supporting tissues, driven by microbial dysbiosis and an exaggerated host immune response. Beyond its local effects, periodontitis has been increasingly associated with systemic conditions, such as cardiovascular disease, diabetes mellitus, chronic kidney disease and stroke, highlighting its broader clinical relevance. Klotho, an anti‑aging and regulatory protein primarily expressed in the kidneys, has emerged as a key regulator of inflammation, oxidative stress and cellular homeostasis. Both circulating soluble Klotho and locally expressed Klotho are considered to contribute to periodontal tissue homeostasis, although the relative contribution of each remains under investigation. Recent evidence suggests that Klotho plays a protective role in periodontal tissues by suppressing inflammatory signaling pathways, including NF‑κB, reducing oxidative stress through antioxidant mechanisms, and supporting cell survival, regeneration and preserving alveolar bone homeostasis Experimental and clinical studies suggest that decreased levels of Klotho may be linked to the progression of periodontal disease, while restoring Klotho levels may offer therapeutic benefits. In addition, Klotho has been shown to function as a potential as a biomarker for disease activity and as a target for regenerative and precision‑based periodontal therapies. Although current evidence remains limited, Klotho represents a promising link between systemic regulation and periodontal health. The present mini review summarizes the biological functions of Klotho, its mechanistic role in periodontitis and its potential diagnostic and therapeutic implications.
View Figures

Figure 1

Klotho in periodontal health and
disease progression. Schematic representation of Klotho in
periodontal health and disease. In health, Klotho reduces
pro-inflammatory cytokines (IL-1β and TNF-α), inhibits NF-κB
signaling, decreases RANKL-mediated osteoclast activity and limits
oxidative stress, maintaining tissue homeostasis. In periodontitis,
reduced Klotho expression due to microbial dysbiosis (e.g.,
Porphyromonas gingivalis) and host immune activation leads
to increased inflammation, NF-κB activation, RANKL-driven
osteoclastogenesis, oxidative stress and periodontal tissue
destruction. IL, interleukin; TNF-α, tumor necrosis factor α;
RANKL, receptor activator of nuclear factor-κB ligand; ROS,
reactive oxygen species.

Figure 2

Klotho in periodontitis: Biomarker
and therapeutic roles. Overview of Klotho as a biomarker and
therapeutic target in periodontitis. Klotho can be detected in
saliva, serum, gingival crevicular fluid, dental plaque and
gingival tissue for risk stratification, early detection, disease
assessment, and treatment monitoring. Therapeutically, nonsurgical
periodontal therapy may be complemented by Klotho-based local drug
delivery, host modulation, and gene therapy-based or stem
cell-based approaches. Increased Klotho activity reduces
inflammatory cytokines, NF-κB signaling, RANKL expression, and
oxidative stress, promoting tissue repair, bone preservation, and
improved periodontal outcomes. IL, interleukin; TNF-α, tumor
necrosis factor α; RANKL, receptor activator of nuclear factor-κB
ligand; GCF, gingival crevicular fluid; NSPT, non-surgical
periodontal therapy; LDD, local drug delivery.
View References

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Spandidos Publications style
Patil GV, Mahendra J and Ponnaiyan D: Klotho in periodontitis: Mechanisms, biomarker potential and therapeutic implications (Review). World Acad Sci J 8: 79, 2026.
APA
Patil, G.V., Mahendra, J., & Ponnaiyan, D. (2026). Klotho in periodontitis: Mechanisms, biomarker potential and therapeutic implications (Review). World Academy of Sciences Journal, 8, 79. https://doi.org/10.3892/wasj.2026.494
MLA
Patil, G. V., Mahendra, J., Ponnaiyan, D."Klotho in periodontitis: Mechanisms, biomarker potential and therapeutic implications (Review)". World Academy of Sciences Journal 8.5 (2026): 79.
Chicago
Patil, G. V., Mahendra, J., Ponnaiyan, D."Klotho in periodontitis: Mechanisms, biomarker potential and therapeutic implications (Review)". World Academy of Sciences Journal 8, no. 5 (2026): 79. https://doi.org/10.3892/wasj.2026.494
Copy and paste a formatted citation
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Spandidos Publications style
Patil GV, Mahendra J and Ponnaiyan D: Klotho in periodontitis: Mechanisms, biomarker potential and therapeutic implications (Review). World Acad Sci J 8: 79, 2026.
APA
Patil, G.V., Mahendra, J., & Ponnaiyan, D. (2026). Klotho in periodontitis: Mechanisms, biomarker potential and therapeutic implications (Review). World Academy of Sciences Journal, 8, 79. https://doi.org/10.3892/wasj.2026.494
MLA
Patil, G. V., Mahendra, J., Ponnaiyan, D."Klotho in periodontitis: Mechanisms, biomarker potential and therapeutic implications (Review)". World Academy of Sciences Journal 8.5 (2026): 79.
Chicago
Patil, G. V., Mahendra, J., Ponnaiyan, D."Klotho in periodontitis: Mechanisms, biomarker potential and therapeutic implications (Review)". World Academy of Sciences Journal 8, no. 5 (2026): 79. https://doi.org/10.3892/wasj.2026.494
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