Mandible-derived extracellular vesicles regulate early tooth development in miniature swine via targeting KDM2B

Abstract

Tissue interactions play a crucial role in tooth development. Notably, extracellular vesicle-mediated interactions between the mandible and tooth germ are considered essential. Here, we revealed that mandible extracellular vesicles could modulate the proliferation and differentiation of dental mesenchymal cells by regulating the histone demethylase KDM2B. Further investigation showed that mandible derived extracellular vesicles could deliver miR-206 to KDM2B, thereby regulating tooth development. An animal study demonstrated that the miR-206/KDM2B pathway affected tooth morphogenesis and mineralization after eight weeks of subcutaneous transplantation in nude mice. In conclusion, this study suggested that the mandible played a critical role in tooth morphogenesis and mineralization, which could be a potential therapeutic target for abnormal tooth development and an alternative model for tooth regeneration.

References

[1] BawaskarHS, BawaskarPH. Oral diseases: a global public health challenge. Lancet, 2020, 395: 185-186.

[2] CelesteRK, et al. . Social mobility and tooth loss: a systematic review and meta-analysis. J. Dent. Res., 2022, 101: 143-150.

[3] ZhangW, YelickPC. Tooth repair and regeneration: potential of dental stem cells. Trends Mol. Med., 2021, 27: 501-511.

[4] LiL, TangQ, WangA, ChenY. Regrowing a tooth: in vitro and in vivo approaches. Curr. Opin. Cell Biol., 2019, 61: 126-131.

[5] HuangD, et al. . Tooth regeneration: insights from tooth development and spatial-temporal control of bioactive drug release. Stem Cell Rev. Rep., 2020, 16: 41-55.

[6] SuiBD, et al. . Mesenchymal condensation in tooth development and regeneration: a focus on translational aspects of organogenesis. Physiol. Rev., 2023, 103: 1899-1964.

[7] Yu T. & Klein O. D. Molecular and cellular mechanisms of tooth development, homeostasis and repair. Development147 (2020).

[8] HuH, et al. . Dental niche cells directly contribute to tooth reconstitution and morphogenesis. Cell Rep., 2022, 41: 111737.

[9] BalicA. Concise review: cellular and molecular mechanisms regulation of tooth initiation. Stem Cells, 2019, 37: 26-32.

[10] Wang F, et al. Tracking diphyodont development in miniature pigs in vitro and in vivo. Biol. Open8, (2019).

[11] IkedaEMR, et al. . Fully functional bioengineered tooth replacement as an organ replacement therapy. Proc. Natl. Acad. Sci. USA, 2009, 106: 13475-13480.

[12] PlavcanJM, DaeglingDJ. Interspecific and intraspecific relationships between tooth size and jaw size in primates. J. Hum. Evol., 2006, 51: 171-184.

[13] LiY, et al. . Mandible exosomal ssc-mir-133b regulates tooth development in miniature swine via endogenous apoptosis. Bone Res., 2018, 6: 28.

[14] LinY, et al. . The epigenetic regulation in tooth development and regeneration. Curr. Stem Cell Res. Ther., 2018, 13: 4-15

[15] HussainA, TebyaniyanH, KhayatanD. The role of epigenetic in dental and oral regenerative medicine by different types of dental stem cells: a comprehensive overview. Stem Cells Int., 2022, 2022: 5304860.

[16] ZhangH, et al. . Epigenetic regulation of methylation in determining the fate of dental mesenchymal stem cells. Stem Cells Int., 2022, 2022: 5015856.

[17] ZhengLW, et al. . Bivalent histone modifications during tooth development. Int. J. Oral. Sci., 2014, 6: 205-211.

[18] LiQM, et al. . Effect of histone demethylase KDM5A on the odontogenic differentiation of human dental pulp cells. Bioengineered, 2020, 11: 449-462.

[19] ChenZ, et al. . lncRNA HOTAIRM1 promotes osteogenesis of hDFSCs by epigenetically regulating HOXA2 via DNMT1 in vitro. J. Cell Physiol., 2020, 235: 8507-8519.

[20] ZhengH, et al. . miR-140-3p enhanced the osteo/odontogenic differentiation of DPSCs via inhibiting KMT5B under hypoxia condition. Int. J. Oral. Sci., 2021, 13: 41.

[21] Baranova J. et al. Tooth formation: are the hardest tissues of human body hard to regenerate? Int. J. Mol. Sci. 21, (2020).

[22] RaoP, JingJ, FanY, ZhouC. Spatiotemporal cellular dynamics and molecular regulation of tooth root ontogeny. Int. J. Oral. Sci., 2023, 15: 50.

[23] DuW, BhojwaniA, HuJK. FACEts of mechanical regulation in the morphogenesis of craniofacial structures. Int. J. Oral. Sci., 2021, 13: 4.

[24] CobourneMT, SharpePT. Tooth and jaw: molecular mechanisms of patterning in the first branchial arch. Arch. Oral. Biol., 2003, 48: 1-14.

[25] AlfaqeehSA, GaeteM, TuckerAS. Interactions of the tooth and bone during development. J. Dent. Res., 2013, 92: 1129-1135.

[26] RenvoiseE, et al. . Mechanical constraint from growing jaw facilitates mammalian dental diversity. Proc. Natl. Acad. Sci. USA, 2017, 114: 9403-9408.

[27] HermansF, et al. . Intertwined signaling pathways governing tooth development: a give-and-take between canonical Wnt and Shh. Front. Cell Dev. Biol., 2021, 9: 758203.

[28] Hosoya A. et al. Sonic Hedgehog signaling and tooth development. Int. J. Mol. Sci. 21, (2020).

[29] KovacsCS, et al. . The role of biomineralization in disorders of skeletal development and tooth formation. Nat. Rev. Endocrinol., 2021, 17: 336-349.

[30] Ono W. et al. Parathyroid hormone receptor signalling in osterix-expressing mesenchymal progenitors is essential for tooth root formation. Nat. Commun. 7, (2016).

[31] DixsonAC, DawsonTR, Di VizioD, WeaverAM. Context-specific regulation of extracellular vesicle biogenesis and cargo selection. Nat. Rev. Mol. Cell Biol., 2023, 24: 454-476.

[32] JiangN, et al. . Exosomes mediate epithelium-mesenchyme crosstalk in organ development. ACS Nano, 2017, 11: 7736-7746.

[33] MeadeMJ, DreyerCW. Tooth agenesis: an overview of diagnosis, aetiology and management. Jpn. Dent. Sci. Rev., 2023, 59: 209-218.

[34] ZhangH, et al. . Tooth number abnormality: from bench to bedside. Int. J. Oral. Sci., 2023, 15: 5.

[35] LeeJM, et al. . MSX1 drives tooth morphogenesis through controlling wnt signaling activity. J. Dent. Res., 2022, 101: 832-839.

[36] ChuKY, et al. . PAX9 mutations and genetic synergism in familial tooth agenesis. Ann. N.Y. Acad. Sci., 2023, 1524: 87-96.

[37] MaoJJ, ProckopDJ. Stem cells in the face: tooth regeneration and beyond. Cell Stem Cell, 2012, 11: 291-301.

[38] HeL, et al. . Parenchymal and stromal tissue regeneration of tooth organ by pivotal signals reinstated in decellularized matrix. Nat. Mater., 2019, 18: 627-637.

[39] ZhangM, et al. . Investigate the odontogenic differentiation and dentin-pulp tissue regeneration potential of neural crest cells. Front. Bioeng. Biotechnol., 2020, 8: 475.

[40] NakaoK, et al. . The development of a bioengineered organ germ method. Nat. Methods, 2007, 4: 227-230.

[41] OshimaM, et al. . Functional tooth regeneration using a bioengineered tooth unit as a mature organ replacement regenerative therapy. PLoS One, 2011, 6. e21531

[42] WangF, et al. . The cell re-association-based whole-tooth regeneration strategies in large animal, Sus scrofa. Cell Prolif., 2018, 51. e12479

[43] LiY, et al. . Deciphering the heterogeneity landscape of mesenchymal stem/stromal cell-derived extracellular vesicles for precise selection in translational medicine. Adv. Health Mater., 2023, 12. e2202453

Funding

National Natural Science Foundation of China (National Science Foundation of China)(82071078)

RIGHTS & PERMISSIONS

The Author(s)