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UBAP2 通过调节成骨细胞生成和破骨细胞生成在骨稳态中发挥作用。

UBAP2 plays a role in bone homeostasis through the regulation of osteoblastogenesis and osteoclastogenesis.

机构信息

Department of Medical Genetics, Ajou University School of Medicine, Suwon, Republic of Korea.

Department of Biomedical Sciences, Ajou University Graduate School of Medicine, Suwon, Republic of Korea.

出版信息

Nat Commun. 2023 Jun 20;14(1):3668. doi: 10.1038/s41467-023-39448-8.

DOI:10.1038/s41467-023-39448-8
PMID:37339951
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10281941/
Abstract

Osteoporosis is a condition characterized by decreased bone mineral density (BMD) and reduced bone strength, leading to an increased risk of fractures. Here, to identify novel risk variants for susceptibility to osteoporosis-related traits, an exome-wide association study is performed with 6,485 exonic single nucleotide polymorphisms (SNPs) in 2,666 women of two Korean study cohorts. The rs2781 SNP in UBAP2 gene is suggestively associated with osteoporosis and BMD with p-values of 6.1 × 10 (odds ratio = 1.72) and 1.1 × 10 in the case-control and quantitative analyzes, respectively. Knockdown of Ubap2 in mouse cells decreases osteoblastogenesis and increases osteoclastogenesis, and knockdown of ubap2 in zebrafish reveals abnormal bone formation. Ubap2 expression is associated with E-cadherin (Cdh1) and Fra1 (Fosl1) expression in the osteclastogenesis-induced monocytes. UBAP2 mRNA levels are significantly reduced in bone marrow, but increased in peripheral blood, from women with osteoporosis compared to controls. UBAP2 protein level is correlated with the blood plasma level of the representative osteoporosis biomarker osteocalcin. These results suggest that UBAP2 has a critical role in bone homeostasis through the regulation of bone remodeling.

摘要

骨质疏松症是一种以骨矿物质密度（BMD）降低和骨强度降低为特征的疾病，导致骨折风险增加。在这里，为了鉴定骨质疏松相关特征易感性的新型风险变异，对来自两个韩国研究队列的 2666 名女性的 6485 个外显子单核苷酸多态性（SNP）进行了外显子全基因组关联研究。UBAP2 基因中的 rs2781 SNP 与骨质疏松症和 BMD 呈显著相关，在病例对照和定量分析中 p 值分别为 6.1×10（比值比=1.72）和 1.1×10。在小鼠细胞中敲低 Ubap2 会减少成骨细胞生成并增加破骨细胞生成，而在斑马鱼中敲低 ubap2 会导致骨形成异常。Ubap2 的表达与破骨细胞诱导的单核细胞中 E-钙黏蛋白（Cdh1）和 Fra1（Fosl1）的表达相关。与对照组相比，骨质疏松症女性的骨髓中 UBAP2 mRNA 水平显著降低，但外周血中水平升高。UBAP2 蛋白水平与代表性骨质疏松生物标志物骨钙素的血浆水平相关。这些结果表明，UBAP2 通过调节骨重塑在骨稳态中具有关键作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d79f/10281941/3851d291a018/41467_2023_39448_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d79f/10281941/ec0cf7b73b51/41467_2023_39448_Fig1_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d79f/10281941/651f0d3b05d8/41467_2023_39448_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d79f/10281941/bbf9a922abbd/41467_2023_39448_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d79f/10281941/b71226528b63/41467_2023_39448_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d79f/10281941/3851d291a018/41467_2023_39448_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d79f/10281941/ec0cf7b73b51/41467_2023_39448_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d79f/10281941/c02bd72842e8/41467_2023_39448_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d79f/10281941/7e189dbd65e3/41467_2023_39448_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d79f/10281941/651f0d3b05d8/41467_2023_39448_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d79f/10281941/bbf9a922abbd/41467_2023_39448_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d79f/10281941/b71226528b63/41467_2023_39448_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d79f/10281941/3851d291a018/41467_2023_39448_Fig7_HTML.jpg

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