Pyruvate dehydrogenase kinase 1-dependent metabolic reprogramming: A promising target for postmenopausal osteoporosis treatment

被引：1

作者：

Xie, Dingbang ^{[1
]}

Xu, Yunteng ^{[1
,2
]}

Zhang, Yimin ^{[1
]}

Cai, Wanping ^{[1
]}

Lan, Xin ^{[1
]}

Yan, Hui ^{[1
]}

机构：

[1] Fujian Univ Tradit Chinese Med, Key Lab Integrat Med Chron Dis, Synthesized Lab Integrat Med, Coll Integrat Med,Lab Pathophysiol,Fujian Prov Uni, Fuzhou, Peoples R China

[2] Fujian Univ Tradit Chinese Med, Acad Integrat Med, Fuzhou, Peoples R China

来源：

BIOMEDICINE & PHARMACOTHERAPY | 2023年 / 160卷

关键词：

Postmenopausal osteoporosis; Osteoclastogenesis; Icariin; Metabolic reprogramming; Pyruvate dehydrogenase subunit alpha pSer 232; Pyruvate dehydrogenase kinase 1; PHOSPHORYLATION; ICARIIN;

D O I：

10.1016/j.biopha.2023.114411

中图分类号：

R-3 [医学研究方法]; R3 [基础医学];

学科分类号：

1001 ;

摘要：

Postmenopausal osteoporosis (PMOP) is a classic endocrine disorder characterized by an imbalance between bone formation and bone resorption. Abnormal glucose metabolic reprogramming has been widely explored in endocrine disorders, but its role in PMOP has not been elucidated. Icariin (ICA), as a bioactive component of the traditional Chinese medicine Epimedium grandiflorum, has been testified to be effective for PMOP treatment, but its effects on glucose metabolism are poorly studied. In this study, pyruvate dehydrogenase was proved to be a key regulator of the metabolic switch in PMOP and the efficacy of ICA. The augmentation of pyruvate dehydrogenase subunit alpha (PDHA) pSer232, which was excited in osteoclasts; the decreased expression of citrate synthase; elevated expression of lactate dehydrogenase; and changes in the pyruvate, lactate, and citrate pools all indicated the preference for aerobic glycolysis in PMOP. Further study showed that the expression and activity of pyruvate dehydrogenase kinase 1 (PDK1) which regulated the phosphorylation status of PDHA Ser232 were both increased in ovariectomized rats. Furthermore, the genetic knockdown of PDK1 and pharmaceutical inhibition of PDK1 markedly suppressed osteoclastogenesis. Meanwhile, ICA might reverse metabolic reprogramming by inhibiting PDK1. In conclusion, this study revealed that PDK1-dependent metabolic reprogramming is a potential therapeutic target for PMOP treatment. ICA alleviates PMOP by inhibiting PDK1 in osteoclasts, indicating its potential for clinical use.

引用

页数：12