Title
Author
DOI
Article Type
Special Issue
Volume
Issue
Exploring the clinical significance of cuproptosis and bone metabolism factors in tooth eruption disturbances
1Department of Stomatology, The Lianyungang Affiliated Hospital of Xuzhou Medical University/Lianyungang First People’s Hospital, 222002 Lianyungang, Jiangsu, China
2Department of Anesthesia, The Maternal and Child Health Hospital of Lianyungang City, 222006 Lianyungang, Jiangsu, China
DOI: 10.22514/jocpd.2026.043 Vol.50,Issue 2,March 2026 pp.142-147
Submitted: 03 August 2025 Accepted: 25 September 2025
Published: 03 March 2026
*Corresponding Author(s): Han Qin E-mail: qinhan2005@163.com
Background: This study aimed to investigate the clinical significance of cuproptosis and bone metabolism factors in tooth eruption disturbances. Methods: Dental follicle tissue and alveolar bone tissue from 10 patients with tooth eruption disturbances were collected as the eruption disturbance group (Group EG). Likewise, corresponding tissues from 10 patients undergoing removal of impacted third molars for orthodontic treatment were collected as the control group (Group CG). Morphological changes in dental follicle cells were evaluated by hematoxylin and eosin (H&E) staining. Protein expression of ferredoxin1 (FDX1), dihydrolipoamide S-acetyltransferase (DLAT), receptor activator of nuclear factor κB ligand (RANKL), and osteoprotegerin (OPG) in dental follicle tissue and alveolar bone tissue was examined by immunohistochemistry (IHC). Results: H&E staining of dental follicle tissue in Group EG showed reduced cell volume and condensed nuclei, suggesting impaired osteoblast/osteoclast differentiation. IHC analysis demonstrated that in Group EG, expression of FDX1, DLAT, and RANKL was reduced in the same direction in both dental follicle tissue and alveolar bone tissue, whereas OPG expression was increased. Consequently, the RANKL/OPG ratio was significantly decreased compared with Group CG. Conclusions: Excessive stress during tooth eruption may alter cuproptosis by affecting cell morphology, thereby disturbing the balance of bone differentiation factors in dental follicle cells and ultimately contributing to eruption disturbances.
Tooth eruption disturbances; Stress; Cuproptosis; Dental follicle tissues; Bone metabolism
Han Qin,Jun Cai. Exploring the clinical significance of cuproptosis and bone metabolism factors in tooth eruption disturbances. Journal of Clinical Pediatric Dentistry. 2026. 50(2);142-147.
[1] Stonehouse-Smith D, Ota L, Seehra J, Kwok J, Liu C, Seppala M, et al. How do teeth erupt? British Dental Journal. 2024; 237: 217–221.
[2] Wagner D, Rey T, Maniere MC, Dubourg S, Bloch-Zupan A, Strub M. Primary failure of eruption: from molecular diagnosis to therapeutic management. Journal of Oral Biology and Craniofacial Research. 2023; 13: 169–176.
[3] Modafferi C, Tabolacci E, Grippaudo C, Chiurazzi P. Syndromic and non-syndromic primary failure of tooth eruption: a genetic overview. Genes. 2025; 16: 147.
[4] Chen JH, Ying Y, Li HM, Sha ZM, Lin JQ, Wu YJ, et al. Abnormal dental follicle cells: a crucial determinant in tooth eruption disorders (Review). Molecular Medicine Reports. 2024; 30: 13292.
[5] Bastos VC, Gomez RS, Gomes CC. Revisiting the human dental follicle: from tooth development to its association with unerupted or impacted teeth and pathological changes. Developmental Dynamics. 2022; 251: 408–423.
[6] Arnst J, Jing Z, Cohen C, Ha SW, Viggeswarapu M, Beck GR III. Bioactive silica nanoparticles target autophagy, NF-κB, and MAPK pathways to inhibit osteoclastogenesis. Biomaterials. 2023; 301: 122238.
[7] Krasnova O, Neganova I. Assembling the puzzle pieces. Insights for in vitro bone remodeling. Stem Cell Reviews and Reports. 2023; 19: 1635–1658.
[8] Liu N, He YQ, Chen XM, Qiu GP, Wu Y, Shen YQ. Changes in cuproptosis-related gene expression in periodontitis: an integrated bioinformatic analysis. Life Sciences. 2024; 338: 122388.
[9] Li DL, Gao ZH, Li Q, Liu XJ, Liu H. Cuproptosis—a potential target for the treatment of osteoporosis. Frontiers in Endocrinology. 2023; 14: 1135181.
[10] Liu N, Chen MB. Crosstalk between ferroptosis and cuproptosis: from mechanism to potential clinical application. Biomedicine & Pharmacotherapy. 2024; 171: 116115.
[11] Benton HM, Butters M, Brous M, Bolon B, Copeland K, Fortin JS, et al. Utilizing image analysis by optical density to evaluate changes in hematoxylin and eosin staining quality after reagent overuse. Journal of Histotechnology. 2025; 48: 123–134.
[12] Hussaini HM, Seo B, Rich AM. Immunohistochemistry and immunofluorescence. Methods in Molecular Biology. 2023; 2588: 439–450.
[13] Lwin CT, Cooney M, Goh M, Tham D, Nowak S. Factors associated with successful surgical exposure of impacted maxillary canines. Journal of Oral and Maxillofacial Surgery. 2024; 82: 93–101.
[14] Del Rio Cantero N, Mourelle Martínez MR, Sagastizabal Cardelús B, De Nova García JM. Influence of zoledronic acid and pamidronate on tooth eruption in children with osteogenesis imperfecta. Bone. 2024; 182: 117069.
[15] Stergiopulos O, Lagou A, Antonarakis GS, Pandis N, Kiliaridis S. The effect of occlusal loading on secondary tooth eruption: an experimental study using a rat model. Journal of Morphology. 2024; 285: e21755.
[16] Muthu MS, Vandana S, Akila G, Anusha M, Kandaswamy D, Aswath Narayanan MB. Global variations in eruption chronology of primary teeth: a systematic review and meta-analysis. Archives of Oral Biology. 2024; 158: 105857.
[17] Topal BG, Tanrikulu A. Assessment of permanent teeth development in children with multiple persistent primary teeth. Journal of Clinical Pediatric Dentistry. 2023; 47: 50–57.
[18] Liu Y, Sun XY, Zhang XL, Wang XZ, Zhang CY, Zheng SG. Runx2 mutation impairs osteogenic differentiation of dental follicle cells. Archives of Oral Biology. 2019; 97: 156–164.
[19] Di CG, Marzano E, Mastrostefano A, Pitocco D, Castilho RS, Zambelli R, et al. The pathogenetic role of RANK/RANKL/OPG signaling in osteoarthritis and related targeted therapies. Biomedicines. 2024; 12: 2292.
[20] El-Masri BM, Andreasen CM, Laursen KS, Kofod VB, Dahl XG, Nielsen MH, et al. Mapping RANKL- and OPG-expressing cells in bone tissue: the bone surface cells as activators of osteoclastogenesis and promoters of the denosumab rebound effect. Bone Research. 2024; 12: 62.
[21] Qin H, Cai J. Effect of periostin on bone metabolic and autophagy factors during tooth eruption in mice. Open Life Sciences. 2023; 18: 20220663.
[22] Gostage J, Kostenuik P, Goljanek-Whysall K, Bellantuono I, McCloskey E, Bonnet N. Extra-osseous roles of the RANK-RANKL-OPG axis with a focus on skeletal muscle. Current Osteoporosis Reports. 2024; 22: 632–650.
[23] Arid J, Xavier TA, da Silva RAB, De Rossi A, da Silva LAB, de Queiroz AM, et al. RANKL is associated with persistent primary teeth and delayed permanent tooth emergence. International Journal of Paediatric Dentistry. 2019; 29: 294–300.
[24] Tsvetkov P, Coy S, Petrova B, Dreishpoon M, Verma A, Abdusamad M, et al. Copper induces cell death by targeting lipoylated TCA cycle proteins. Science. 2022; 375: 1254–1261.
[25] Lei G, Sun MC, Cheng J, Ye R, Lu ZZ, Horbath A, et al. Radiotherapy promotes cuproptosis and synergizes with cuproptosis inducers to overcome tumor radioresistance. Cancer Cell. 2025; 43: 1076–1092.
[26] Tian SP, Wang R, Wang YT, Chen RB, Lin TY, Xiao XS, et al. p32 regulates glycometabolism and TCA cycle to inhibit ccRCC progression via copper-induced DLAT lipoylation oligomerization. International Journal of Biological Sciences. 2024; 20: 516–536.
[27] Lu JY, Ling X, Sun YH, Liu L, Liu L, Wang XY, et al. FDX1 enhances endometriosis cell cuproptosis via G6PD-mediated redox homeostasis. Apoptosis. 2023; 28: 1128–1140.
[28] Liu SY, Ge JY, Chu YT, Cai SY, Wu J, Gong AX, et al. Identification of hub cuproptosis related genes and immune cell infiltration characteristics in periodontitis. Frontiers in Immunology. 2023; 14: 1164667.
[29] Han JJ, Luo JY, Wang CJ, Kapilevich L, Zhang XA. Roles and mechanisms of copper homeostasis and cuproptosis in osteoarticular diseases. Biomedicine & Pharmacotherapy. 2024; 174: 116570.
Top