Evidence map›Paper›PMID 40914424›Full record

ArticleJournal of advanced research2026

HDAC3 represses Nrf2-GDF11 signaling to drive chondrocyte adipogenesis in temporomandibular joint osteoarthritis.

Yuqian Shi, Zhihua Xu, Fuyin Li, Qian Liu, Ying Zhan, Fan Wu, Qinghua Li, Fa He, Peinan Fan, Hongyun Zhang and 4 more

Abstract read
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Article in Journal of advanced research, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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1 · What the graph read from it

What it found

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2 · The registry

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3 · Its place in the literature

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4 · The record

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5 · Who and what money

Authors and funding

14 authors.

Yuqian ShiState Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, National Clinical Research Center for Oral Diseases, Shaanxi International Joint Research Center for Oral Diseases, Department of Oral Anatomy and Physiology and TMD, School of Stomatology, The Fourth Military Medical University, Xi'an 710032, China.
Zhihua XuState Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, National Clinical Research Center for Oral Diseases, Shaanxi International Joint Research Center for Oral Diseases, Department of Oral Anatomy and Physiology and TMD, School of Stomatology, The Fourth Military Medical University, Xi'an 710032, China.
Fuyin LiState Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, National Clinical Research Center for Oral Diseases, Shaanxi International Joint Research Center for Oral Diseases, Department of Oral Anatomy and Physiology and TMD, School of Stomatology, The Fourth Military Medical University, Xi'an 710032, China.
Qian LiuDepartment of Stomatology, Air Force Medical Center, PLA, Beijing 100142, China.
Ying ZhanState Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, National Clinical Research Center for Oral Diseases, Shaanxi International Joint Research Center for Oral Diseases, Department of Oral Anatomy and Physiology and TMD, School of Stomatology, The Fourth Military Medical University, Xi'an 710032, China.
Fan WuState Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, National Clinical Research Center for Oral Diseases, Shaanxi International Joint Research Center for Oral Diseases, Department of Oral Anatomy and Physiology and TMD, School of Stomatology, The Fourth Military Medical University, Xi'an 710032, China.
Qinghua LiState Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, National Clinical Research Center for Oral Diseases, Shaanxi International Joint Research Center for Oral Diseases, Department of Oral Anatomy and Physiology and TMD, School of Stomatology, The Fourth Military Medical University, Xi'an 710032, China.
Fa HeState Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers and National Clinical Research Center for Digestive Diseases, Xijing Hospital of Digestive Diseases, The Fourth Military Medical University, Xi'an 710032, China.
Peinan FanState Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, National Clinical Research Center for Oral Diseases, Shaanxi International Joint Research Center for Oral Diseases, Department of Oral Anatomy and Physiology and TMD, School of Stomatology, The Fourth Military Medical University, Xi'an 710032, China.
Hongyun ZhangState Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, National Clinical Research Center for Oral Diseases, Shaanxi International Joint Research Center for Oral Diseases, Department of Oral Anatomy and Physiology and TMD, School of Stomatology, The Fourth Military Medical University, Xi'an 710032, China.
Shibin YuState Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, National Clinical Research Center for Oral Diseases, Shaanxi International Joint Research Center for Oral Diseases, Department of Oral Anatomy and Physiology and TMD, School of Stomatology, The Fourth Military Medical University, Xi'an 710032, China.
Feng HeState Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, National Clinical Research Center for Oral Diseases, Shaanxi Clinical Research Center for Oral Diseases, Department of Oral and Maxillofacial Surgery, School of Stomatology, The Fourth Military Medical University, Xi'an 710032, China. Electronic address: hefengfmmu@qq.com.
Helin WangState Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, National Clinical Research Center for Oral Diseases, Department of Medical Rehabilitation, School of Stomatology, The Fourth Military Medical University, Xi'an 710032, China. Electronic address: 921441502@qq.com.
Mian ZhangState Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, National Clinical Research Center for Oral Diseases, Shaanxi International Joint Research Center for Oral Diseases, Department of Oral Anatomy and Physiology and TMD, School of Stomatology, The Fourth Military Medical University, Xi'an 710032, China. Electronic address: zhangmian1986@aliyun.com.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

introductionAberrant biomechanical force-induced chondrocyte adipogenesis is involved in the development of temporomandibular joint osteoarthritis (TMJ OA). Growth differentiation factor 11 (GDF11) has been implicated in this process. However, whether mechanosensitive histone deacetylase 3 (HDAC3) regulates GDF11 signaling in the context of TMJ OA remains to be elucidated.

objectiveTo elucidate the HDAC3-mediated regulation of GDF11 during chondrocyte adipogenesis in TMJ OA.

methodsA unilateral anterior crossbite (UAC) rat model and cyclic tensile strain (CTS)-stimulated ATDC5 cells were established to mimic aberrant biomechanical force. Cartilage degeneration was assessed via Safranin O staining and qRT-PCR. Chondrocyte adipogenesis was evaluated using Oil Red O staining, transmission electron microscopy (TEM), and Adiponectin immunohistochemistry (IHC). The expression of HDAC3, nuclear factor erythroid 2-related factor 2 (Nrf2), and GDF11 was quantified by IHC, qRT-PCR, and western blotting. The binding of Nrf2 to GDF11 was evaluated by dual-luciferase reporter assays. The therapeutic interventions included intra-articular injections of the HDAC3 inhibitor RGFP966 (10 mg/kg) and the Nrf2 agonist Bardoxolone (10 mg/kg).

resultsThe articular cartilage was significantly thinner, the modified Osteoarthritis Research Society International (OARSI) scores were increased, the expression of cartilage matrix markers (collagen II and aggrecan) was reduced, and the expression of chondrocyte hypertrophic markers (collagen X, matrix metalloprotease-13, and alkaline phosphatase) was increased in the UAC-induced OA model group compared with the sham control group. Excessive biomechanical force accelerated chondrocyte adipogenesis, as indicated by increased lipid droplet accumulation and Adiponectin upregulation. Concurrently, HDAC3 was upregulated, which suppressed Nrf2 and downregulated GDF11. Dual-luciferase reporter assays confirmed the direct binding of Nrf2 to the GDF11 promoter in chondrocytes. Treatment with the HDAC3 inhibitor RGFP966 or the Nrf2 agonist Bardoxolone restored GDF11 expression, significantly attenuating adipogenesis and alleviating cartilage degeneration.

conclusionsOur findings indicate that aberrant biomechanical force induces HDAC3 upregulation, which suppresses Nrf2-mediated transactivation of GDF11, thereby promoting chondrocyte adipogenesis and exacerbating TMJ OA progression.

Indexed as

AdipogenesisBiomechanical PhenomenaChondrocytesGrowth Differentiation FactorsHistone Deacetylase 3NF-E2-Related Factor 2Temporomandibular Joint DisordersAnimalsDisease ProgressionFemaleGene Expression RegulationOsteoarthritisRatsRats, Sprague-DawleySignal TransductionStress, MechanicalGdf11 protein, ratGrowth Differentiation FactorsHistone Deacetylase 3Nfe2l2 protein, ratNF-E2-Related Factor 2Aberrant biomechanical forceChondrocyte adipogenesisHDAC3Nrf2Osteoarthritis

Identifiers

PMID40914424
PMCPMC13227241

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.