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소장정보 검색

국회도서관 홈으로 정보검색 소장정보 검색
결과 내 검색 동의어 포함
결과 내 검색 동의어 포함

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Bone homeostasis is maintained by an intricate balance between osteoclasts and osteoblasts, which becomes disturbed in osteoporosis. Metallothioneins (MTs) are major contributors in cellular zinc regulation. However, the role of MTs in bone cell regulation has remained unexplored. Single-cell RNA sequencing analysis discovered that, unlike the expression of other MT members, the expression of MT3 was unique to osteoclasts among various macrophage populations and was highly upregulated during osteoclast differentiation. This unique MT3 upregulation was validated experimentally and supported by ATAC sequencing data analyses. Downregulation of MT3 by gene knockdown or knockout resulted in excessive osteoclastogenesis and exacerbated bone loss in ovariectomy-induced osteoporosis. Transcriptome sequencing of MT3 knockdown osteoclasts and gene set enrichment analysis indicated that the oxidative stress and redox pathways were enriched, which was verified by MT3-dependent regulation of reactive oxygen species (ROS). In addition, MT3 deficiency increased the transcriptional activity of SP1 in a manner dependent on intracellular zinc levels. This MT3-zinc-SP1 axis was crucial for the control of osteoclasts, as zinc chelation and SP1 knockdown abrogated the promotion of SP1 activity and osteoclastogenesis by MT3 deletion. Moreover, SP1 bound to the NFATc1 promoter, and overexpression of an inactive SP1 mutant negated the effects of MT3 deletion on NFATc1 and osteoclastogenesis. In conclusion, MT3 plays a pivotal role in controlling osteoclastogenesis and bone metabolism via dual axes involving ROS and SP1. The present study demonstrated that MT3 elevation is a potential therapeutic strategy for osteolytic bone disorders, and it established for the first time that MT3 is a crucial bone mass regulator.

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기사명 저자명 페이지 원문 목차
Tailored antisense oligonucleotides designed to correct aberrant splicing reveal actionable groups of mutations for rare genetic disorders Htoo A. Wai, Eliska Svobodova, Natalia Romero Herrera, Andrew G.L. Douglas, John W. Holloway, Francisco E. Baralle, Marco Baralle, Diana Baralle p. 1-10

Astrocytic 5-HT1A receptor mediates age-dependent hippocampal LTD and fear memory extinction in male mice Qian-Yun Wu, Lian-Hong Lin, Kun Lu, Si-Fu Deng, Wei-Min Li, Yuan Xu, Bin Zhang, Ji-Hong Liu p. 1-13

(The) potential role of gut microbiota-derived metabolites as regulators of metabolic syndrome-associated mitochondrial and endolysosomal dysfunction in Alzheimer’s disease Young Hyun Jung, Chang Woo Chae, Ho Jae Han p. 1-12

Comprehensive molecular characterization of TFE3-rearranged renal cell carcinoma Cho-Rong Lee, Jungyo Suh, Dongjun Jang, Bo-Yeong Jin, Jaeso Cho, Moses Lee, Hyungtai Sim, Minyong Kang, Jueun Lee, Ju Hyun Park ... [et al.] p. 1-9

Low-level brain somatic mutations in exonic regions are collectively implicated in autism with germline mutations in autism risk genes Il Bin Kim, Myeong-Heui Kim, Saehoon Jung, Woo Kyeong Kim, Junehawk Lee, Young Seok Ju, Maree J. Webster, Sanghyeon Kim, Ja Hye Kim, Hyun Jung Kim, Junho Kim, Sangwoo Kim, Jeong Ho Lee p. 1-13

Inhibition of BCAT1-mediated cytosolic leucine metabolism regulates Th17 responses via the mTORC1-HIF1α pathway Yeon Jun Kang, Woorim Song, Su Jeong Lee, Seung Ah Choi, Sihyun Chae, Bo Ruem Yoon, Hee Young Kim, Jung Ho Lee, Chulwoo Kim, Joo-Youn Cho, Hyun Je Kim, Won-Woo Lee p. 1-15

Neutrophil extracellular traps mediate the crosstalk between plaque microenvironment and unstable carotid plaque formation Yu Cao, Minghui Chen, Xinyu Jiao, Shuijie Li, Dong Wang, Yongxuan Zhan, Jiaju Li, Zhongfei Hao, Qingbin Li, Yang Liu ... [et al.] p. 1-19

(A) neutrophil elastase-generated mature form of IL-33 is a potent regulator of endothelial cell activation and proliferative retinopathy Shivantika Bisen, Shailendra Kumar Verma, Chandra Sekhar Mukhopadhyay, Nikhlesh K. Singh p. 1-14

SMC3 contributes to heart development by regulating super-enhancer associated genes Bowen Zhang, Yongchang Zhu, Zhen Zhang, Feizhen Wu, Xiaojing Ma, Wei Sheng, Ranran Dai, Zhenglong Guo, Weili Yan, Lili Hao, Guoying Huang, Duan Ma, Bingtao Hao, Jing Ma p. 1-17

Unique expression and critical role of metallothionein 3 in the control of osteoclastogenesis and osteoporosis Shenzheng Mo, Min Kyung Kim, Ji Sun Jang, Seung Hye Lee, Seo Jin Hong, Suhan Jung, Hong-Hee Kim p. 1-16

(A) dual inhibitor of PIP5K1C and PIKfyve prevents SARS-CoV-2 entry into cells Yuri Seo, Yejin Jang, Seon-gyeong Lee, Joon Ho Rhlee, Sukyeong Kong, Thi Tuyet Hanh Vo, Myung hun Kim, Myoung Kyu Lee, Byungil Kim, Sung You Hong, Meehyein Kim, Joo-Yong Lee, Kyungjae Myung p. 1-14

(The) Foxo1-YAP-Notch1 axis reprograms STING-mediated innate immunity in NASH progression Dongwei Xu, Xiaoye Qu, Tao Yang, Mingwei Sheng, Xiyun Bian, Yongqiang Zhan, Yizhu Tian, Yuanbang Lin, Yuting Jin, Xiao Wang ... [et al.] p. 1-13

Altered lipid metabolism promoting cardiac fibrosis is mediated by CD34+ cell-derived FABP4+ fibroblasts Luping Du, Xuyang Wang, Yan Guo, Tingting Tao, Hong Wu, Xiaodong Xu, Bohuan Zhang, Ting Chen, Qingbo Xu, Xiaogang Guo p. 1-18

Clinical application of whole-genome sequencing of solid tumors for precision oncology Ryul Kim, Seokhwi Kim, Brian Baek-Lok Oh, Woo Sik Yu, Chang Woo Kim, Hoon Hur, Sang-Yong Son, Min Jae Yang, Dae Sung Cho, Taeyang Ha ... [et al.] p. 1-13

참고문헌 (62건) : 자료제공( 네이버학술정보 )

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