Hypoxic dental pulp stem cells-released succinate promotes osteoclastogenesis and root resorption

Yang, Andi; Wang, Jinmeng; Yang, Zhiyu; Wang, Lulu; Li, Houxuan; Lei, Lang

doi:10.7150/ijms.94972

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Int J Med Sci 2024; 21(6):1155-1164. doi:10.7150/ijms.94972 This issue Cite

Research Paper

Hypoxic dental pulp stem cells-released succinate promotes osteoclastogenesis and root resorption

Andi Yang^1,2, Jinmeng Wang², Zhiyu Yang², Lulu Wang^1,2, Houxuan Li^1✉, Lang Lei^1,2✉

1. Nanjing Stomatological Hospital, Affiliated Hospital of Medical School of Nanjing University, Nanjing, China.
2. Central Laboratory of Stomatology, Nanjing Stomatological Hospital, Affiliated Hospital of Medical School of Nanjing University, Nanjing, China.

Citation:

Yang A, Wang J, Yang Z, Wang L, Li H, Lei L. Hypoxic dental pulp stem cells-released succinate promotes osteoclastogenesis and root resorption. Int J Med Sci 2024; 21(6):1155-1164. doi:10.7150/ijms.94972. https://www.medsci.org/v21p1155.htm

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Abstract

Introduction: Clinical studies have shown that endodontically-treated nonvital teeth exhibit less root resorption during orthodontic tooth movement. The purpose of this study was to explore whether hypoxic dental pulp stem cells (DPSCs) can promote osteoclastogenesis in orthodontically induced inflammatory root resorption (OIIRR).

Methods: Succinate in the supernatant of DPSCs under normal and hypoxic conditions was measured by a succinic acid assay kit. The culture supernatant of hypoxia-treated DPSCs was used as conditioned medium (Hypo-CM). Bone marrow-derived macrophages (BMDMs) from succinate receptor 1 (SUCNR1)-knockout or wild-type mice were cultured with conditioned medium (CM), exogenous succinate or a specific inhibitor of SUCNR1 (4c). Tartrate-resistant acid phosphatase (TRAP) staining, Transwell assays, qPCR, Western blotting, and resorption assays were used to evaluate osteoclastogenesis-related changes.

Results: The concentration of succinate reached a maximal concentration at 6 h in the supernatant of hypoxia-treated DPSCs. Hypo-CM-treated macrophages were polarized to M1 proinflammatory macrophages. Hypo-CM treatment significantly increased the formation and differentiation of osteoclasts and increased the expression of osteoclastogenesis-related genes, and this effect was inhibited by the specific succinate inhibitor 4c. Succinate promoted chemotaxis and polarization of M1-type macrophages with increased expression of osteoclast generation-related genes. SUCNR1 knockout decreased macrophage migration, M1 macrophage polarization, differentiation and maturation of osteoclasts, as shown by TRAP and NFATc1 expression and cementum resorption.

Conclusions: Hypoxic DPSC-derived succinate may promote osteoclast differentiation and root resorption. The regulation of the succinate-SUCNR1 axis may contribute to the reduction in the OIIRR.

Keywords: Dental pulp stem cells, root resorption, hypoxia, succinate

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APA

Yang, A., Wang, J., Yang, Z., Wang, L., Li, H., Lei, L. (2024). Hypoxic dental pulp stem cells-released succinate promotes osteoclastogenesis and root resorption. International Journal of Medical Sciences, 21(6), 1155-1164. https://doi.org/10.7150/ijms.94972.

ACS

Yang, A.; Wang, J.; Yang, Z.; Wang, L.; Li, H.; Lei, L. Hypoxic dental pulp stem cells-released succinate promotes osteoclastogenesis and root resorption. Int. J. Med. Sci. 2024, 21 (6), 1155-1164. DOI: 10.7150/ijms.94972.

NLM

CSE

Yang A, Wang J, Yang Z, Wang L, Li H, Lei L. 2024. Hypoxic dental pulp stem cells-released succinate promotes osteoclastogenesis and root resorption. Int J Med Sci. 21(6):1155-1164.

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