期刊
BONE
卷 46, 期 3, 页码 604-612出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.bone.2009.11.007
关键词
Postmenopausal women; Osteoporosis; Gene expression profiling; BMD; Bone
资金
- SouthEastern Norway Regional Health Authority
- Ullevaal University Hospital [29750104]
- Norwegian Osteoporosis Society
- Norwegian Research Council
- Anders Jahre's Foundation for Promotion of Science
- Rachel and Otto Brunns Legate
- Novo Nordisk Foundation
- European Union [FP6-502491]
Low bone mineral density (BMD) is an important risk factor for skeletal fractures which Occur in about 40% of women >= 50 years in the western world. We describe the transcriptional changes in 84 trans-iliacal bone biopsies associated with BMD variations in postmenopausal females (50 to 86 years), aiming to identify genetic determinants of bone Structure. The women were healthy OF having a primary osteopenic or osteoporotic status with or without low energy fractures. The total cohort of 91 unrelated women representing a wide range of BMDs, were consecutively registered and submitted to global gene Affymetrix microarray expression analysis or histomorphometry. Among almost 23,000 expressed transcripts, a set represented by ACSL3 (acyl-CoA synthetase long-chain family member 3), NIPSNAP3B (nipsnap homolog 313), DLEU2 (Deleted in lymphocytic leukemia, 2), C1ORF61 (Chromosome I open reading frame 61), DKK1 (Dickkopf homolog 1), SOST (Sclerostin), ABCA8, (ATP-binding cassette, sub-family A, member 8), and uncharacterized (AFFX-M27830-M-at), was significantly correlated to total hip BMD (5% false discovery rate) explaining 62% of the BMD variation expressed as T-score, 53% when adjusting for the influence of age (Z-score) and 44% when further adjusting for body mass index (BMI). Only SOST was previously associated to BMD, and the majority of the genes have previously not been associated with a bone phenotype. In molecular network analyses, SOST shows a strong, positive correlation with DKK1, both being members of the Wnt signaling pathway. The results provide novel insight in the underlying biology of bone metabolism and osteoporosis which is the ultimate consequence of low BMD. (C) 2009 Elsevier Inc. All rights reserved.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据