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Role of IL-17 in Periodontitis and Immune Response
Interleukin-17 (IL-17) is a pivotal cytokine that plays a dual role in the pathogenesis of periodontitis and in the maintenance of bone health. It is primarily produced by T-helper 17 (Th17) cells, which are crucial for host defense against microbial infections, particularly in the oral cavity. IL-17 facilitates the recruitment of neutrophils and enhances their function, which is essential for combating bacterial invasion during periodontitis (Tang et al., 2025). However, the overexpression of IL-17 can lead to chronic inflammation and tissue destruction, resulting in significant alveolar bone resorption, a hallmark of periodontitis (Tang et al., 2025).
In the context of periodontitis, IL-17 is induced within the gingival tissues in response to microbial dysbiosis, particularly by pathogens such as Porphyromonas gingivalis. This dysbiosis activates immune responses that contribute to the inflammatory milieu, fostering an environment conducive to chronic inflammatory processes (Huo et al., 2025). The persistence of IL-17 in the periodontium underlines its complex role in both protective immunity and pathological processes, emphasizing the need for a balanced IL-17 response to maintain periodontal health and prevent bone loss.
Mechanisms of IL-17-Induced Bone Resorption
IL-17’s role in bone metabolism is characterized by its capacity to induce osteoclastogenesis, the process of forming osteoclasts that resorb bone. Key mechanisms involve the upregulation of receptor activator of nuclear factor kappa B ligand (RANKL) expression by osteoblasts and fibroblast-like synoviocytes (FLS) in response to IL-17 stimulation. This RANKL promotes osteoclast differentiation and activation, leading to increased bone resorption (Li et al., 2025). Moreover, IL-17 also stimulates the production of pro-inflammatory cytokines such as TNF-α and IL-1β, which further exacerbate osteoclast activity and contribute to bone loss in inflammatory conditions (Tang et al., 2025).
In rheumatoid arthritis (RA), IL-17 has been shown to similarly enhance bone resorption through mechanisms that amplify osteoclast activity. The interaction between IL-17, RANKL, and other pro-inflammatory mediators forms a feedback loop that perpetuates inflammation and bone destruction (Huo et al., 2025). This dual role of IL-17 in promoting both protective immune responses and pathological bone resorption underscores the complexity of targeting IL-17 in therapeutic strategies for periodontitis and RA.
Relationship Between IL-17 and Osteoporosis in RA Patients
Recent studies have highlighted a significant relationship between IL-17 levels and the risk of developing osteoporosis in patients with rheumatoid arthritis. The inflammatory environment characteristic of RA, largely driven by elevated IL-17, contributes to systemic bone loss and osteoporosis (Li et al., 2025). Osteoporosis in RA patients often correlates with disease severity, with increased IL-17 levels serving as a biomarker for potential bone density reduction (Huo et al., 2025).
The IL-17-mediated activation of osteoclasts through RANKL signaling is a critical pathway linking RA to osteoporosis. Patients with RA exhibit higher levels of IL-17, which correlates with increased osteoclastogenesis and subsequent bone resorption (Huo et al., 2025). This association suggests that therapeutic interventions targeting IL-17 may not only help manage inflammatory symptoms of RA but also mitigate the risk of osteoporosis and related fractures in affected individuals.
IL-17’s Dual Effect on Bone Regeneration and Destruction
The dual nature of IL-17 in bone health—promoting both regeneration and destruction—presents a therapeutic challenge. In the context of bone regeneration, IL-17 can stimulate the proliferation and differentiation of mesenchymal stem cells into osteoblasts, thereby supporting bone healing processes (Tang et al., 2025). This regenerative aspect is particularly evident in fracture healing models, where IL-17 plays a role in promoting osteoblast activity and enhancing new bone formation (Huo et al., 2025).
Conversely, in chronic inflammatory conditions such as periodontitis and RA, the pathological overproduction of IL-17 leads to excessive osteoclast activation and bone loss. This highlights the necessity for a nuanced understanding of IL-17’s role in different physiological versus pathological contexts. Therapeutic strategies must therefore aim to modulate IL-17 activity, enhancing its beneficial effects while mitigating its deleterious impacts on bone health (Huo et al., 2025).
Therapeutic Strategies Targeting IL-17 in Periodontal Disease
Given the central role of IL-17 in periodontitis and its implications for bone health, targeting this cytokine presents a promising therapeutic avenue. Various strategies are being explored, including the use of monoclonal antibodies that specifically inhibit IL-17 or its signaling pathways. For instance, agents such as secukinumab and ixekizumab have shown efficacy in reducing IL-17-mediated inflammation in autoimmune diseases, suggesting potential applications in periodontitis management (Tang et al., 2025).
Additionally, combination therapies that include anti-inflammatory agents and IL-17 inhibitors may offer synergistic benefits in controlling periodontal inflammation and promoting bone preservation. These approaches aim to balance the immune response to effectively combat the bacterial triggers of periodontitis while protecting against the inflammatory damage that leads to bone loss (Huo et al., 2025).
Table 1: Summary of IL-17 Effects on Bone Health
| Function | Protective Role | Pathological Role |
|---|---|---|
| Bone Formation | Promotes osteoblast differentiation | Inhibits bone formation in chronic disease |
| Osteoclast Regulation | Modulates RANKL expression | Enhances osteoclastogenesis in inflammation |
| Immune Response | Supports neutrophil recruitment | Drives chronic inflammation |
| Tissue Repair | Facilitates bone regeneration | Contributes to bone loss |
FAQs
What is the role of IL-17 in periodontitis?
IL-17 plays a dual role in periodontitis by enhancing immune responses to bacterial infections while also contributing to tissue destruction and bone loss when produced in excess.
How does IL-17 affect bone health in rheumatoid arthritis patients?
Elevated IL-17 levels in RA patients are associated with increased osteoclast activity and bone resorption, contributing to a higher risk of osteoporosis.
Can targeting IL-17 be a therapeutic strategy for periodontal disease?
Yes, therapies that inhibit IL-17 have shown promise in reducing inflammation and may help preserve bone health in periodontal disease.
What are the implications of IL-17 for bone regeneration?
While IL-17 can stimulate bone regeneration under certain conditions, its overexpression in chronic inflammation can lead to detrimental effects, highlighting the need for therapeutic modulation.
References
- Tang, Z., Jin, L., & Yang, Y. (2025). The dual role of IL-17 in periodontitis regulating immunity and bone homeostasis. Frontiers in Immunology, 14, 1578635. https://doi.org/10.3389/fimmu.2025.1578635
- Huo, X., Peng, Y., Li, H., Li, C., Liao, F., Miao, C., & Huang, Y. (2025). The emerging role of vascular endothelial cell-mediated angiogenesis in the imbalance of RA synovial microenvironment and its clinical relevance. Frontiers in Pharmacology, 14, 1481089. https://doi.org/10.3389/fphar.2025.1481089
- Li, J., Bao, L., Dai, C., & He, M. (2025). Exploring the causal relationship between osteoporosis and rheumatoid arthritis: A bidirectional Mendelian randomization study. Orthopedic Research and Reviews, 17, 48–55. https://doi.org/10.2147/ORR.S508155
