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Review
. 2025 Jun 26:12:1581446.
doi: 10.3389/fmed.2025.1581446. eCollection 2025.

Energy metabolism dysfunction and therapeutic strategies for treating temporomandibular disorders

Wenjie Gao #  1 , Zhiheng Gao #  1 , Heting Xiao #  1 , Yuchen Qian #  1 , Rongkang Fan  1 , Yonggang Li  1 , Shaofeng Yang  1 , Yanjun Yang  2 , Yusen Qiao  1
Affiliations
Review

Energy metabolism dysfunction and therapeutic strategies for treating temporomandibular disorders

Wenjie Gao et al. Front Med (Lausanne). .

Abstract

Temporomandibular disorders (TMD) are prevalent and multifactorial conditions affecting the temporomandibular joint (TMJ). Recent studies have highlighted the central role of energy metabolism in their pathogenesis. This review focuses on how disturbances in glucose, lipid, and mitochondrial energy pathways contribute to TMJ dysfunction and degeneration. The TMJ's complex structure relies heavily on a balanced energy supply to maintain its physiological functions. Disruptions in glucose metabolism lead to oxidative stress, inflammatory cytokine release, and chondrocyte damage. Similarly, altered lipid metabolism-particularly imbalances in ω-3 and ω-6 fatty acids-modifies inflammatory responses. Hormonal influences, including cholesterol and estrogen, further exacerbate joint degeneration via signaling pathways such as Notch and NF-κB. These metabolic disturbances trigger cellular senescence, impaired matrix synthesis, and structural breakdown of cartilage and bone. The review also evaluates current and emerging therapeutic strategies. Standard treatments such as NSAIDs and corticosteroids relieve symptoms but fail to address underlying metabolic dysfunctions. Promising alternatives include intra-articular growth factors, metabolic modulators targeting oxidative stress, and autophagy inducers that restore mitochondrial balance. These approaches aim to correct cellular energy imbalances and support tissue regeneration. TMD involve significant metabolic dysregulation in the TMJ. Understanding the role of energy metabolism offers new insights into disease mechanisms and potential therapies. Future research should prioritize metabolic regulation as a target for long-term and disease-modifying treatments in TMD management.

Keywords: energy metabolism; metabolic dysregulation; temporomandibular disorders; temporomandibular joint; therapeutic strategies.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Overview of the effects of energy metabolism on the TMJ.
Figure 2
Figure 2
Mechanism of NOX4-mediated TMJ inflammation and therapeutic role of GLX351322.
Figure 3
Figure 3
Mechanism of notch signaling activation and its modulation by metabolic and inflammatory factors.
Figure 4
Figure 4
Hyaluronic acid metabolism in normal TMJ.
Figure 5
Figure 5
Changes of signal pathway in TMJ under mechanical stress.
See this image and copyright information in PMC

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