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Effects of 4-hexylresorcinol on facial skeletal development in growing rats: Considerations for diabetes

  • Hannah Jeong (Department of Orthodontics, College of Dentistry, Gangneung-Wonju National University) ;
  • Jwa-Young Kim (Department of Oral and Maxillofacial Surgery, Hallym University Kangnam Sacred Heart Hospital, Hallym University Medical Center) ;
  • Xiangguo Che (Department of Biochemistry and Cell Biology, Cell and Matrix Research Institute, Korea Mouse Phenotyping Center, School of Medicine, Kyungpook National University) ;
  • Je-Yong Choi (Department of Biochemistry and Cell Biology, Cell and Matrix Research Institute, Korea Mouse Phenotyping Center, School of Medicine, Kyungpook National University) ;
  • Insan Jang (Department of Orthodontics, College of Dentistry, Gangneung-Wonju National University) ;
  • Seong-Gon Kim (Department of Oral and Maxillofacial Surgery, College of Dentistry, Gangneung-Wonju National University)
  • Received : 2023.04.25
  • Accepted : 2023.08.29
  • Published : 2023.11.25

Abstract

Objective: To investigate the long-term effects of 4-hexylresorcinol (4HR) on facial skeletal growth in growing male rats, with a focus on diabetic animal models. Methods: Forty male rats were used. Of them, type 1 diabetes mellitus was induced in 20 animals by administering 40 mg/kg streptozotocin (STZ), and they were assigned to either the STZ or 4HR-injected group (STZ/4HR group). The remaining 20 healthy rats were divided into control and 4HR groups. We administered 4HR subcutaneously at a weekly dose of 10 mg/kg until the rats were euthanized. At 16 weeks of age, whole blood was collected, and microcomputed tomography of the skull and femur was performed. Results: All craniofacial linear measurements were smaller in the STZ group than in the control group. The mandibular molar width was significantly smaller in the 4HR group than in the control group (P = 0.031) but larger in the STZ/4HR group than in the STZ group (P = 0.011). Among the diabetic animals, the STZ/4HR group exhibited significantly greater cortical bone thickness, bone mineral density, and bone volume than the STZ group. Serum testosterone levels were also significantly higher in the STZ/4HR group than in the STZ group. Conclusions: 4HR administration may have divergent effects on mandibular growth and bone mass in healthy and diabetic rats. In the context of diabetes, 4HR appears to have beneficial effects, potentially through the modulation of mitochondrial respiration.

Keywords

Acknowledgement

The animal experiments were supported by Prof. Ji-Hyeon Oh and Dr. Yei-Jin Kang.

References

  1. Manlove AE, Romeo G, Venugopalan SR. Craniofacial growth: current theories and influence on management. Oral Maxillofac Surg Clin North Am 2020;32:167-75. https://doi.org/10.1016/j.coms.2020.01.007
  2. Nonaka K, Nakata M. Genetic and environmental factors in the longitudinal growth of rats: III. Craniofacial shape change. J Craniofac Genet Dev Biol 1988;8:337-44. https://pubmed.ncbi.nlm.nih.gov/3220936/
  3. Varrela J. Genetic and epigenetic regulation of craniofacial development. Proc Finn Dent Soc 1991;87:239-44. https://pubmed.ncbi.nlm.nih.gov/1896436/
  4. De Clerck HJ, Proffit WR. Growth modification of the face: a current perspective with emphasis on Class III treatment. Am J Orthod Dentofacial Orthop 2015;148:37-46. https://doi.org/10.1016/j.ajodo.2015.04.017
  5. Frankel R, Frankel C. A functional approach to treatment of skeletal open bite. Am J Orthod 1983;84:54-68. https://doi.org/10.1016/0002-9416(83)90148-3
  6. Bannister AJ, Kouzarides T. Regulation of chromatin by histone modifications. Cell Res 2011;21:381-95. https://doi.org/10.1038/cr.2011.22
  7. Roth SY, Denu JM, Allis CD. Histone acetyltransferases. Annu Rev Biochem 2001;70:81-120. https://doi.org/10.1146/annurev.biochem.70.1.81
  8. Adithya SP, Balagangadharan K, Selvamurugan N. Epigenetic modifications of histones during osteoblast differentiation. Biochim Biophys Acta Gene Regul Mech 2022;1865:194780. https://doi.org/10.1016/j.bbagrm.2021.194780
  9. Yi SJ, Lee H, Lee J, Lee K, Kim J, Kim Y, et al. Bone remodeling: histone modifications as fate determinants of bone cell differentiation. Int J Mol Sci 2019;20:3147. https://doi.org/10.3390/ijms20133147
  10. Cho HH, Park HT, Kim YJ, Bae YC, Suh KT, Jung JS. Induction of osteogenic differentiation of human mesenchymal stem cells by histone deacetylase inhibitors. J Cell Biochem 2005;96:533-42. https://doi.org/10.1002/jcb.20544
  11. Schroeder TM, Westendorf JJ. Histone deacetylase inhibitors promote osteoblast maturation. J Bone Miner Res 2005;20:2254-63. https://doi.org/10.1359/JBMR.050813
  12. Kim JY, Kweon HY, Kim DW, Choi JY, Kim SG. 4-Hexylresorcinol inhibits class I histone deacetylases in human umbilical cord endothelial cells. Appl Sci 2021;11:3486. https://doi.org/10.3390/app11083486
  13. Choi KH, Kim DW, Lee SK, Kim SG, Kim TW. The administration of 4-Hexylresorcinol accelerates orthodontic tooth movement and increases the expression level of bone turnover markers in ovariectomized rats. Int J Mol Sci 2020;21:1526. https://doi.org/10.3390/ijms21041526
  14. Lee IS, Kim DW, Oh JH, Lee SK, Choi JY, Kim SG, et al. Effects of 4-Hexylresorcinol on craniofacial growth in rats. Int J Mol Sci 2021;22:8935. https://doi.org/10.3390/ijms22168935
  15. Pitteloud N, Mootha VK, Dwyer AA, Hardin M, Lee H, Eriksson KF, et al. Relationship between testosterone levels, insulin sensitivity, and mitochondrial function in men. Diabetes Care 2005;28:1636-42. https://doi.org/10.2337/diacare.28.7.1636
  16. Wada J, Nakatsuka A. Mitochondrial dynamics and mitochondrial dysfunction in diabetes. Acta Med Okayama 2016;70:151-8. https://doi.org/10.18926/AMO/54413
  17. Sangwung P, Petersen KF, Shulman GI, Knowles JW. Mitochondrial dysfunction, insulin resistance, and potential genetic implications. Endocrinology 2020;161:bqaa017. https://doi.org/10.1210/endocr/bqaa017
  18. Sifuentes-Franco S, Pacheco-Moises FP, Rodriguez-Carrizalez AD, Miranda-Diaz AG. The role of oxidative stress, mitochondrial function, and autophagy in diabetic polyneuropathy. J Diabetes Res 2017;2017:1673081. https://doi.org/10.1155/2017/1673081
  19. Lee IS, Chang JH, Kim DW, Kim SG, Kim TW. The effect of 4-hexylresorinol administration on NAD+ level and SIRT activity in Saos-2 cells. Maxillofac Plast Reconstr Surg 2021;43:39. https://doi.org/10.1186/s40902-021-00326-2
  20. Ghodsi M, Larijani B, Keshtkar AA, Nasli-Esfahani E, Alatab S, Mohajeri-Tehrani MR. Mechanisms involved in altered bone metabolism in diabetes: a narrative review. J Diabetes Metab Disord 2016;15:52. https://doi.org/10.1186/s40200-016-0275-1
  21. Starup-Linde J, Vestergaard P. Biochemical bone turnover markers in diabetes mellitus - a systematic review. Bone 2016;82:69-78. https://doi.org/10.1016/j.bone.2015.02.019
  22. Qi S, He J, Han H, Zheng H, Jiang H, Hu CY, et al. Anthocyanin-rich extract from black rice (Oryza sativa L. Japonica) ameliorates diabetic osteoporosis in rats. Food Funct 2019;10:5350-60. https://doi.org/10.1039/c9fo00681h
  23. Starup-Linde J. Diabetes, biochemical markers of bone turnover, diabetes control, and bone. Front Endocrinol (Lausanne) 2013;4:21. https://doi.org/10.3389/fendo.2013.00021
  24. Yao S, Du Z, Xiao L, Yan F, Ivanovski S, Xiao Y. Morphometric changes of osteocyte lacunar in diabetic pig mandibular cancellous bone. Biomolecules 2022;13:49. https://doi.org/10.3390/biom13010049
  25. Mohamad NV, Soelaiman IN, Chin KY. A concise review of testosterone and bone health. Clin Interv Aging 2016;11:1317-24. https://doi.org/10.2147/CIA.S115472
  26. Wang N, Wang L, Huang C. Association of total testosterone status with bone mineral density in adults aged 40-60 years. J Orthop Surg Res 2021;16:612. https://doi.org/10.1186/s13018-021-02714-w
  27. Chen H, Chan DC. Mitochondrial dynamics in regulating the unique phenotypes of cancer and stem cells. Cell Metab 2017;26:39-48. https://doi.org/10.1016/j.cmet.2017.05.016
  28. Kim JY, Kim DW, Lee SK, Choi JY, Che X, Kim SG et al. Increased expression of TGF-β1 by 4-hexylresorcinol is mediated by endoplasmic reticulum and mitochondrial stress in human umbilical endothelial vein cells. Appl Sci 2021;11:9128. https://doi.org/10.3390/app11199128
  29. Kim SG. 4-Hexylresorcinol: pharmacologic chaperone and its application for wound healing. Maxillofac Plast Reconstr Surg 2022;44:5. https://doi.org/10.1186/s40902-022-00334-w
  30. Brownlee M. Biochemistry and molecular cell biology of diabetic complications. Nature 2001;414:813-20. https://doi.org/10.1038/414813a