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

Jeonghyun Kim, Bo-Young Kim, Jeong-Soo Lee, Yun-Mi Jeong, Hyun-Ju Cho, Eunkuk Park, Dowan Kim, Sung-Soo Kim, Bom-Taeck Kim, Yong Jun Choi, Ye-Yeon Won, Hyun-Seok Jin (), Yoon-Sok Chung () and Seon-Yong Jeong ()
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Jeonghyun Kim: Ajou University School of Medicine
Bo-Young Kim: Korea Centers for Disease Control & Prevention
Jeong-Soo Lee: Sungkyunkwan University School of Medicine
Yun-Mi Jeong: Korea Research Institute of Bioscience and Biotechnology
Hyun-Ju Cho: Korea Research Institute of Bioscience and Biotechnology
Eunkuk Park: Ajou University School of Medicine
Dowan Kim: Ajou University School of Medicine
Sung-Soo Kim: Hoseo University
Bom-Taeck Kim: Ajou University School of Medicine
Yong Jun Choi: Ajou University School of Medicine
Ye-Yeon Won: Ajou University School of Medicine
Hyun-Seok Jin: Hoseo University
Yoon-Sok Chung: Ajou University School of Medicine
Seon-Yong Jeong: Ajou University School of Medicine

Nature Communications, 2023, vol. 14, issue 1, 1-16

Abstract: 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 × 10−7 (odds ratio = 1.72) and 1.1 × 10−7 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.

Date: 2023
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DOI: 10.1038/s41467-023-39448-8

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