ALKBH5-mediated m6A demethylation of HS3ST3B1-IT1 prevents osteoarthritis

被引：10

作者：

Tang, Yuting ^{[1
,2
]}

Liu, Yang ^{[3
]}

Zhu, Xiaoshu ^{[1
]}

Chen, Yanlin ^{[1
]}

Jiang, Xinluan ^{[1
]}

Ding, Siyang ^{[1
]}

Zheng, Que ^{[1
]}

Zhang, Ming ^{[1
]}

Yang, Jiashu ^{[1
]}

Ma, Yunfei ^{[1
]}

Xing, Mengying ^{[1
]}

Zhang, Zongyu ^{[4
]}

Ding, Huimin ^{[5
]}

Jin, Yucui ^{[1
,2
]}

Ma, Changyan ^{[1
,2
]}

机构：

[1] Nanjing Med Univ, Dept Med Genet, Longmian Rd 101, Nanjing, Peoples R China

[2] Nanjing Med Univ, Jiangsu Key Lab Xenotransplantat, Longmian Rd 101, Nanjing, Peoples R China

[3] Nanjing First Hosp, Dept Orthoped, Nanjing, Peoples R China

[4] Tradit Chinese Med Hosp Lianyungang, Dept Orthoped, Lianyungang, Peoples R China

[5] Nanjing Med Univ, Affiliated BenQ Hosp, BenQ Med Ctr, Dept Orthoped, Nanjing, Peoples R China

来源：

ISCIENCE | 2023年 / 26卷 / 10期

基金：

中国国家自然科学基金;

关键词：

LONG NONCODING RNA; GENOME REGULATION; YTH DOMAIN; REVEALS;

D O I：

10.1016/j.isci.2023.107838

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

HS3ST3B1-IT1 was identified as a downregulated long noncoding RNA in osteoarthritic cartilage. However, its roles and mechanisms in the pathogenesis of osteoarthritis (OA) are unclear. In this study, we demonstrated that the expressions of HS3ST3B1-IT1 and its maternal gene HS3ST3B1 were downregulated and positively correlated in osteoarthritic cartilage. Overexpression of HS3ST3B1-IT1 significantly increased chondrocyte viability, inhibited chondrocyte apoptosis, and upregulated extracellular matrix (ECM) proteins, whereas HS3ST3B1-IT1 knockdown had the opposite effects. In addition, HS3ST3B1IT1 significantly ameliorated monosodium-iodoacetate-induced OA in vivo. Mechanistically, HS3ST3B1IT1 upregulated HS3ST3B1 expression by blocking its ubiquitination-mediated degradation. Knockdown of HS3ST3B1 reversed the effects of HS3ST3B1-IT1 on chondrocyte viability, apoptosis, and ECM metabolism. AlkB homolog 5 (ALKBH5)-mediated N6-methyladenosine (m6A) demethylation stabilized HS3ST3B1-IT1 RNA. Together, our data revealed that ALKBH5-mediated upregulation of HS3ST3B1-IT1 suppressed OA progression by elevating HS3ST3B1 expression, suggesting that HS3ST3B1-IT1/ HS3ST3B1 may serve as potential therapeutic targets for OA treatment.

引用

页数：22

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