Energy metabolism dysfunction and therapeutic strategies for treating temporomandibular disorders

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...

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Main Authors: Wenjie Gao, Zhiheng Gao, Heting Xiao, Yuchen Qian, Rongkang Fan, Yonggang Li, Shaofeng Yang, Yanjun Yang, Yusen Qiao
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-06-01
Series:Frontiers in Medicine
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Online Access:https://www.frontiersin.org/articles/10.3389/fmed.2025.1581446/full
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author Wenjie Gao
Zhiheng Gao
Heting Xiao
Yuchen Qian
Rongkang Fan
Yonggang Li
Shaofeng Yang
Yanjun Yang
Yusen Qiao
author_facet Wenjie Gao
Zhiheng Gao
Heting Xiao
Yuchen Qian
Rongkang Fan
Yonggang Li
Shaofeng Yang
Yanjun Yang
Yusen Qiao
author_sort Wenjie Gao
collection DOAJ
description 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.
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spelling doaj-art-c20f7ef1f6fc4667b933a55c8191020a2025-08-20T03:30:36ZengFrontiers Media S.A.Frontiers in Medicine2296-858X2025-06-011210.3389/fmed.2025.15814461581446Energy metabolism dysfunction and therapeutic strategies for treating temporomandibular disordersWenjie Gao0Zhiheng Gao1Heting Xiao2Yuchen Qian3Rongkang Fan4Yonggang Li5Shaofeng Yang6Yanjun Yang7Yusen Qiao8Department of Orthopedics, The First Affiliated Hospital of Soochow University, Suzhou, ChinaDepartment of Orthopedics, The First Affiliated Hospital of Soochow University, Suzhou, ChinaDepartment of Orthopedics, The First Affiliated Hospital of Soochow University, Suzhou, ChinaDepartment of Orthopedics, The First Affiliated Hospital of Soochow University, Suzhou, ChinaDepartment of Orthopedics, The First Affiliated Hospital of Soochow University, Suzhou, ChinaDepartment of Orthopedics, The First Affiliated Hospital of Soochow University, Suzhou, ChinaDepartment of Orthopedics, The First Affiliated Hospital of Soochow University, Suzhou, ChinaDepartment of Orthopedics, Suzhou Ninth People’s Hospital Afffliated to Soochow University, Suzhou, ChinaDepartment of Orthopedics, The First Affiliated Hospital of Soochow University, Suzhou, ChinaTemporomandibular 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.https://www.frontiersin.org/articles/10.3389/fmed.2025.1581446/fullenergy metabolismtemporomandibular jointtemporomandibular disorderstherapeutic strategiesmetabolic dysregulation
spellingShingle Wenjie Gao
Zhiheng Gao
Heting Xiao
Yuchen Qian
Rongkang Fan
Yonggang Li
Shaofeng Yang
Yanjun Yang
Yusen Qiao
Energy metabolism dysfunction and therapeutic strategies for treating temporomandibular disorders
Frontiers in Medicine
energy metabolism
temporomandibular joint
temporomandibular disorders
therapeutic strategies
metabolic dysregulation
title Energy metabolism dysfunction and therapeutic strategies for treating temporomandibular disorders
title_full Energy metabolism dysfunction and therapeutic strategies for treating temporomandibular disorders
title_fullStr Energy metabolism dysfunction and therapeutic strategies for treating temporomandibular disorders
title_full_unstemmed Energy metabolism dysfunction and therapeutic strategies for treating temporomandibular disorders
title_short Energy metabolism dysfunction and therapeutic strategies for treating temporomandibular disorders
title_sort energy metabolism dysfunction and therapeutic strategies for treating temporomandibular disorders
topic energy metabolism
temporomandibular joint
temporomandibular disorders
therapeutic strategies
metabolic dysregulation
url https://www.frontiersin.org/articles/10.3389/fmed.2025.1581446/full
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