颞下颌关节骨关节炎病理性钙化机制及精准防治策略

doi:10.13591/j.cnki.kqyx.2025.08.001

口腔医学 ›› 2025, Vol. 45 ›› Issue (8): 561-566.doi: 10.13591/j.cnki.kqyx.2025.08.001

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颞下颌关节骨关节炎病理性钙化机制及精准防治策略

韩潇潇, 覃文聘, 焦凯()

空军军医大学唐都医院口腔科, 陕西西安 (710038)

收稿日期:2025-04-26 出版日期:2025-08-28 发布日期:2025-08-21
通讯作者: 焦凯 E-mail:kjiao1@163.com
作者简介:焦凯,空军军医大学第二附属医院(唐都医院)口腔科主任、支部书记、口腔医学教研室主任、主任医师、教授,博士生导师,为国务院特殊津贴专家,国家“万人计划”青年拔尖人才,全球前2%顶尖科学家,军队青年科技英才,陕西省杰青,陕西省科技新星,空军高层次人才,国家人才项目和国家自然科学基金同行评审专家。主要从事颞下颌关节疾病防治和修复重建策略研究,主持国家重点研发计划课题2项、国家自然科学基金5项、国临中心重点项目2项及军队后勤重点研发等课题。近5年,以通信作者发表科技论文52篇,单篇最高IF为32.085分,IF>10分的20篇。获中华口腔医学会科技一等奖、陕西省科技一等奖、全国发明展览会金奖、中国医疗器械创新创业大赛二等奖、陕西省科技创新团队等。获授权国际发明专利3项,国家专利26项,其中16项为第一发明人。兼任陕西省口腔医师协会副会长,陕西省颞下颌关节病学专委会首任主委。
基金资助:
国家重点研发计划资助(2023YFC2509100);国家自然科学基金面上项目(82471000)

Pathological calcification in temporomandibular joint osteoarthritis: Mechanisms and targeted therapeutic strategies

HAN Xiaoxiao, QIN Wenpin, JIAO Kai()

Department of Stomatology, Tangdu Hospital, Air Force Medical University, Xi’an 710038, China

Received:2025-04-26 Online:2025-08-28 Published:2025-08-21

摘要/Abstract

摘要：

颞下颌关节骨关节炎(TMJ-OA)是以关节软骨退变、疼痛及功能障碍为特征的慢性疾病,病理性钙化作为其核心病理标志,与疾病进展密切相关。近年研究表明,病理性钙化通过改变软骨生物力学特性、激活炎症反应及基质降解通路,加速关节破坏。本文系统综述病理性钙化在TMJ-OA发病中的关键作用,重点探讨关键信号通路、自噬源性钙化囊泡、溶酶体失稳态、细胞器的交互作用等分子机制,并总结药物治疗、基因治疗及纳米技术等新型干预策略,为TMJ-OA的精准防治提供理论依据。

关键词: 病理性钙化, 骨关节炎, 软骨细胞, 钙化囊泡

Abstract:

Temporomandibular joint osteoarthritis(TMJ-OA) is a chronic disorder characterized by degeneration of articular cartilage, pain, and functional impairment, with pathological calcification serving as a central pathological hallmark closely associated with disease progression. Recent studies have demonstrated that pathological calcification accelerates joint destruction by altering cartilage biomechanical properties, activating inflammatory responses, and promoting matrix degradation pathways. This review systematically reviews the critical role of pathological calcification in the pathogenesis of temporomandibular joint osteoarthritis(TMJ-OA), with a focus on molecular mechanisms including key signaling pathways, autophagy-derived calcifying vesicles, lysosomal destabilization and organelle crosstalk. It further summarizes novel intervention strategies such as pharmacological treatments, gene therapy, and nanotechnology-based approaches, thereby providing a theoretical foundation for the precise prevention and treatment of TMJ-OA.

Key words: pathological calcification, osteoarthritis, chondrocyte, calcified vesicles

中图分类号:

R782.6

韩潇潇, 覃文聘, 焦凯. 颞下颌关节骨关节炎病理性钙化机制及精准防治策略[J]. 口腔医学, 2025, 45(8): 561-566.

HAN Xiaoxiao, QIN Wenpin, JIAO Kai. Pathological calcification in temporomandibular joint osteoarthritis: Mechanisms and targeted therapeutic strategies[J]. Stomatology, 2025, 45(8): 561-566.

参考文献 49

[1]	Qin WP, Wan QQ, Yan JF, et al. Effect of extracellular ribonucleic acids on neurovascularization in osteoarthritis[J]. Adv Sci(Weinh), 2023, 10(26): e2301763.
[2]	Sun JL, Yan JF, Yu SB, et al. microRNA-29b promotes subchondral bone loss in TMJ osteoarthritis[J]. J Dent Res, 2020, 99(13): 1469-1477.
[3]	Katz JN, Arant KR, Loeser RF. Diagnosis and treatment of hip and knee osteoarthritis: A review[J]. JAMA, 2021, 325(6): 568-578. doi: 10.1001/jama.2020.22171 pmid: 33560326
[4]	Kloppenburg M, Berenbaum F. Osteoarthritis year in review 2019: Epidemiology and therapy[J]. Osteoarthritis Cartilage, 2020, 28(3): 242-248.
[5]	Ma ZY, Wan QQ, Qin WP, et al. Effect of regional crosstalk between sympathetic nerves and sensory nerves on temporomandibular joint osteoarthritic pain[J]. Int J Oral Sci, 2025, 17(1): 3. doi: 10.1038/s41368-024-00336-6 pmid: 39762209
[6]	Qin WP, Ma ZY, Bai G, et al. Neurovascularization inhibiting dual responsive hydrogel for alleviating the progression of osteoarthritis[J]. Nat Commun, 2025, 16(1): 1390.
[7]	Vidavsky N, Kunitake JAMR, Estroff LA. Multiple pathways for pathological calcification in the human body[J]. Adv Healthc Mater, 2021, 10(4): e2001271.
[8]	Singh A, Tandon S, Tandon C. An update on vascular calcification and potential therapeutics[J]. Mol Biol Rep, 2021, 48(1): 887-896. doi: 10.1007/s11033-020-06086-y pmid: 33394226
[9]	Attiq A, Afzal S, Ahmad W, et al. Hegemony of inflammation in atherosclerosis and coronary artery disease[J]. Eur J Pharmacol, 2024, 966: 176338.
[10]	Alhashmi M, Gremida AME, Maharana SK, et al. Skeletal progenitor LRP1 deficiency causes severe and persistent skeletal defects with Wnt pathway dysregulation[J]. Bone Res, 2025, 13(1): 17. doi: 10.1038/s41413-024-00393-x pmid: 39865089
[11]	Albini A, Di Paola L, Mei G, et al. Inflammation and cancer cell survival: TRAF2 as a key player[J]. Cell Death Dis, 2025, 16(1): 292.
[12]	Vecchio E, Gallo R, Mimmi S, et al. FABP5 is a key player in metabolic modulation and NF-κB dependent inflammation driving pleural mesothelioma[J]. Commun Biol, 2025, 8(1): 324. doi: 10.1038/s42003-025-07754-0 pmid: 40016284
[13]	Khan H, Singh A, Singh Y, et al. Pharmacological modulation of PI3K/PTEN/Akt/mTOR/ERK signaling pathways in ischemic injury: A mechanistic perspective[J]. Metab Brain Dis, 2025, 40(3): 131. doi: 10.1007/s11011-025-01543-8 pmid: 40009091
[14]	Abbass MMS, Rady D, El Moshy S, et al. The temporomandibular joint and the human body: A new perspective on cross talk[J]. Dent J(Basel), 2024, 12(11): 357.
[15]	Abhishek A, Doherty M. Update on calcium pyrophosphate deposition[J]. Clin Exp Rheumatol, 2016, 34(4Suppl 98): 32-38.
[16]	Ea HK, Chobaz V, Nguyen C, et al. Pathogenic role of basic calcium phosphate crystals in destructive arthropathies[J]. PLoS One, 2013, 8(2): e57352.
[17]	McCarthy GM, Dunne A. Calcium crystal deposition diseases: Beyond gout[J]. Nat Rev Rheumatol, 2018, 14(10): 592-602.
[18]	Fuerst M, Niggemeyer O, Lammers L, et al. Articular cartilage mineralization in osteoarthritis of the hip[J]. BMC Musculoskelet Disord, 2009, 10: 166.
[19]	Hawellek T, Hubert J, Hischke S, et al. Articular cartilage calcification of the humeral head is highly prevalent and associated with osteoarthritis in the general population[J]. J Orthop Res, 2016, 34(11): 1984-1990. doi: 10.1002/jor.23227 pmid: 26970411
[20]	Lotz M, Hashimoto S, Kühn K. Mechanisms of chondrocyte apoptosis[J]. Osteoarthritis Cartilage, 1999, 7(4): 389-391.
[21]	张勉, 杨鸿旭, 刘晓东, 等. 软骨细胞CaSR在异常生物力诱导的颞下颌关节骨关节炎中的作用研究[C]//中华口腔医学会第十五次全国颞下颌关节病学及牙合学学术研讨会论文汇编. 昆明,2018: 93.
[22]	Han MS, Jung YK, Kim GW, et al. Transglutaminase-2 regulates Wnt and FoxO3a signaling to determine the severity of osteoarthritis[J]. Sci Rep, 2020, 10(1): 13228.
[23]	Fam AG, Morava-Protzner I, Purcell C, et al. Acceleration of experimental lapine osteoarthritis by calcium pyrophosphate microcrystalline synovitis[J]. Arthritis Rheum, 1995, 38(2): 201-210.
[24]	Yahara Y, Takemori H, Okada M, et al. Pterosin B prevents chondrocyte hypertrophy and osteoarthritis in mice by inhibiting Sik3[J]. Nat Commun, 2016, 7: 10959. doi: 10.1038/ncomms10959 pmid: 27009967
[25]	Sun YB, Franklin AM, Mauerhan DR, et al. Biological effects of phosphocitrate on osteoarthritic articular chondrocytes[J]. Open Rheumatol J, 2017, 11: 62-74. doi: 10.2174/1874312901711010062 pmid: 28659999
[26]	McCarthy GM, Mitchell PG, Struve JA, et al. Basic calcium phosphate crystals cause coordinate induction and secretion of collagenase and stromelysin[J]. J Cell Physiol, 1992, 153(1): 140-146. pmid: 1325976
[27]	Bai G, Howell DS, Howard GA, et al. Basic calcium phosphate crystals up-regulate metalloproteinases but down-regulate tissue inhibitor of metalloproteinase-1 and-2 in human fibroblasts[J]. Osteoarthritis Cartilage, 2001, 9(5): 416-422.
[28]	Pu PD, Ma QY, Wang WS, et al. Protein-degrading enzymes in osteoarthritis[J]. Z Orthop Unfall, 2021, 159(1): 54-66.
[29]	王海英, 丁晓, 杨立, 等. 不同分期骨关节炎关节液中相关降解酶的表达差异[J]. 中国组织工程研究, 2019, 23(23): 3609-3615.
[30]	徐凡, 满城. 蛋白聚糖酶在骨关节炎中的研究进展[J]. 临床口腔医学杂志, 2018, 34(6): 381-383.
[31]	Ye T, Wang CY, Yan JF, et al. Lysosomal destabilization: A missing link between pathological calcification and osteoarthritis[J]. Bioact Mater, 2023, 34: 37-50.
[32]	Yan JF, Shen MJ, Sui BD, et al. Autophagic LC3⁺ calcified extracellular vesicles initiate cartilage calcification in osteoarthritis[J]. Sci Adv, 2022, 8(19): eabn1556.
[33]	Rosenthal AK. Basic calcium phosphate crystal-associated musculoskeletal syndromes: An update[J]. Curr Opin Rheumatol, 2018, 30(2): 168-172. doi: 10.1097/BOR.0000000000000477 pmid: 29227355
[34]	Goldring MB, Goldring SR. Osteoarthritis[J]. J Cell Physiol, 2007, 213(3): 626-634. doi: 10.1002/jcp.21258 pmid: 17786965
[35]	Molloy ES, Morgan MP, McDonnell B, et al. BCP crystals increase prostacyclin production and upregulate the prostacyclin receptor in OA synovial fibroblasts: Potential effects on mPGES1 and MMP-13[J]. Osteoarthritis Cartilage, 2007, 15(4): 414-420.
[36]	Yan JF, Qin WP, Xiao BC, et al. Pathological calcification in osteoarthritis: An outcome or a disease initiator?[J]. Biol Rev Camb Philos Soc, 2020, 95(4): 960-985.
[37]	Di Nicola V. Degenerative osteoarthritis a reversible chronic disease[J]. Regen Ther, 2020, 15: 149-160. doi: 10.1016/j.reth.2020.07.007 pmid: 33426213
[38]	Moyer RF, Ratneswaran A, Beier F, et al. Osteoarthritis year in review 2014: Mechanics: Basic and clinical studies in osteoarthritis[J]. Osteoarthritis Cartilage, 2014, 22(12): 1989-2002.
[39]	Nia HT, Gauci SJ, Azadi M, et al. High-bandwidth AFM-based rheology is a sensitive indicator of early cartilage aggrecan degradation relevant to mouse models of osteoarthritis[J]. J Biomech, 2015, 48(1): 162-165. doi: 10.1016/j.jbiomech.2014.11.012 pmid: 25435386
[40]	Carlson AK, McCutchen CN, June RK. Mechanobiological implications of articular cartilage crystals[J]. Curr Opin Rheumatol, 2017, 29(2): 157-162. doi: 10.1097/BOR.0000000000000368 pmid: 27941391
[41]	Yan JF, Gao B, Wang CY, et al. Calcified apoptotic vesicles from PROCR⁺ fibroblasts initiate heterotopic ossification[J]. J Extracell Vesicles, 2024, 13(4): e12425.
[42]	Han XX, Gao CH, Lu WC, et al. Macrophage-derived extracellular DNA initiates heterotopic ossification[J]. Inflammation, 2023, 46(6): 2225-2240. doi: 10.1007/s10753-023-01873-8 pmid: 37458919
[43]	Gao CH, Wan QQ, Yan JF, et al. Exploring the link between autophagy-lysosomal dysfunction and early heterotopic ossification in tendons[J]. Adv Sci(Weinh), 2024, 11(28): e2400790.
[44]	Lu WC, Yan JF, Wang CY, et al. Interorgan communication in neurogenic heterotopic ossification: The role of brain-derived extracellular vesicles[J]. Bone Res, 2024, 12(1): 11. doi: 10.1038/s41413-023-00310-8 pmid: 38383487
[45]	Lv H, Luo H, Tan W, et al. Kurarinone mitigates LPS-induced inflammatory osteolysis by inhibiting osteoclastogenesis through the reduction of ROS levels and suppression of the PI3K/AKT signaling pathway[J/OL]. Inflammation, (2025-01-27)[2025-04-26].doi:10.1007/S10753-025-02244-1.
[46]	Zhou YF, Li JT, Zheng QL, et al. METTL3-mediated m⁶ A methylation of TRAF5 inhibits lung adenocarcinoma cell metastasisactivation of the PI3K/AKT/NF-κB signaling pathway[J]. Kaohsiung J Med Sci, 2024, 40(2): 150-160.
[47]	Peng WJ, Song YS, Zhu GP, et al. FGF10 attenuates allergic airway inflammation in asthma by inhibiting PI3K/AKT/NF-κBpathway[J]. Cell Signal, 2024, 113: 110964.
[48]	Wang Y, Li ZB, Yu RQ, et al. Metal-phenolic network biointerface-mediated cell regulation for bone tissue regeneration[J]. Mater Today Bio, 2024, 30: 101400.
[49]	Ding TT, Shen WQ, Tao WH, et al. Curcumol ameliorates alcohol and high-fat diet-induced fatty liver diseasemodulation of the Ceruloplasmin/iron overload/mtDNA signaling pathway[J]. J Nutr Biochem, 2025, 136: 109807.

颞下颌关节骨关节炎病理性钙化机制及精准防治策略

Pathological calcification in temporomandibular joint osteoarthritis: Mechanisms and targeted therapeutic strategies

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