RRC ID 76398
著者 Kim J, Kim BY, Lee JS, Jeong YM, Cho HJ, Park E, Kim D, Kim SS, Kim BT, Choi YJ, Won YY, Jin HS, Chung YS, Jeong SY.
タイトル UBAP2 plays a role in bone homeostasis through the regulation of osteoblastogenesis and osteoclastogenesis.
ジャーナル Nat Commun
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.
巻・号 14(1)
ページ 3668
公開日 2023-6-20
DOI 10.1038/s41467-023-39448-8
PII 10.1038/s41467-023-39448-8
PMID 37339951
PMC PMC10281941
MeSH Animals Bone Density / genetics Female Fractures, Bone* / genetics Mice Osteogenesis / genetics Osteoporosis* / genetics Osteoporosis* / metabolism Zebrafish
IF 12.121
リソース情報
ヒト・動物細胞 MC3T3-E1(RCB1126)