One-carbon metabolism supports S-adenosylmethionine and m6A methylation to control the osteogenesis of bone marrow stem cells and bone formation.

Autor:	Zhang W; Hospital of Stomatology, Sun Yat-sen University, Guangzhou 510055, China.; Guangdong Provincial Key Laboratory of Stomatology, Guangzhou 510055, China.; Guanghua School of Stomatology, Sun Yat-sen University, Guangzhou 510055, China., Bai Y; Hospital of Stomatology, Sun Yat-sen University, Guangzhou 510055, China.; Guangdong Provincial Key Laboratory of Stomatology, Guangzhou 510055, China.; Guanghua School of Stomatology, Sun Yat-sen University, Guangzhou 510055, China., Hao L; Hospital of Stomatology, Sun Yat-sen University, Guangzhou 510055, China.; Guangdong Provincial Key Laboratory of Stomatology, Guangzhou 510055, China.; Guanghua School of Stomatology, Sun Yat-sen University, Guangzhou 510055, China., Zhao Y; Hospital of Stomatology, Sun Yat-sen University, Guangzhou 510055, China.; Guangdong Provincial Key Laboratory of Stomatology, Guangzhou 510055, China.; Guanghua School of Stomatology, Sun Yat-sen University, Guangzhou 510055, China., Zhang L; Hospital of Stomatology, Sun Yat-sen University, Guangzhou 510055, China.; Guangdong Provincial Key Laboratory of Stomatology, Guangzhou 510055, China.; Guanghua School of Stomatology, Sun Yat-sen University, Guangzhou 510055, China., Ding W; Hospital of Stomatology, Sun Yat-sen University, Guangzhou 510055, China.; Guangdong Provincial Key Laboratory of Stomatology, Guangzhou 510055, China.; Guanghua School of Stomatology, Sun Yat-sen University, Guangzhou 510055, China., Qi Y; Hospital of Stomatology, Sun Yat-sen University, Guangzhou 510055, China.; Guangdong Provincial Key Laboratory of Stomatology, Guangzhou 510055, China.; Guanghua School of Stomatology, Sun Yat-sen University, Guangzhou 510055, China., Xu Q; Hospital of Stomatology, Sun Yat-sen University, Guangzhou 510055, China.; Guangdong Provincial Key Laboratory of Stomatology, Guangzhou 510055, China.; Guanghua School of Stomatology, Sun Yat-sen University, Guangzhou 510055, China.
Jazyk:	angličtina
Zdroj:	Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research [J Bone Miner Res] 2024 Sep 02; Vol. 39 (9), pp. 1356-1370.
DOI:	10.1093/jbmr/zjae121
Abstrakt:	The skeleton is a metabolically active organ undergoing continuous remodeling initiated by bone marrow stem cells (BMSCs). Recent research has demonstrated that BMSCs adapt the metabolic pathways to drive the osteogenic differentiation and bone formation, but the mechanism involved remains largely elusive. Here, using a comprehensive targeted metabolome and transcriptome profiling, we revealed that one-carbon metabolism was promoted following osteogenic induction of BMSCs. Methotrexate (MTX), an inhibitor of one-carbon metabolism that blocks S-adenosylmethionine (SAM) generation, led to decreased N6-methyladenosine (m6A) methylation level and inhibited osteogenic capacity. Increasing intracellular SAM generation through betaine addition rescued the suppressed m6A content and osteogenesis in MTX-treated cells. Using S-adenosylhomocysteine (SAH) to inhibit the m6A level, the osteogenic activity of BMSCs was consequently impeded. We also demonstrated that the pro-osteogenic effect of m6A methylation mediated by one-carbon metabolism could be attributed to HIF-1α and glycolysis pathway. This was supported by the findings that dimethyloxalyl glycine rescued the osteogenic potential in MTX-treated and SAH-treated cells by upregulating HIF-1α and key glycolytic enzymes expression. Importantly, betaine supplementation attenuated MTX-induced m6A methylation decrease and bone loss via promoting the abundance of SAM in rat. Collectively, these results revealed that one-carbon metabolite SAM was a potential promoter in BMSC osteogenesis via the augmentation of m6A methylation, and the cross talk between metabolic reprogramming, epigenetic modification, and transcriptional regulation of BMSCs might provide strategies for bone regeneration. (© The Author(s) 2024. Published by Oxford University Press on behalf of the American Society for Bone and Mineral Research. All rights reserved. For permissions, please email: journals.permissions@oup.com.)
Databáze:	MEDLINE
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