MRC Harwell Institute, Mammalian Genetics Unit, Harwell Campus, Oxfordshire, United Kingdom.
German Mouse Clinic, Institute of Experimental Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health GmbH, Neuherberg, Germany.
PLoS Genet. 2020 Dec 28;16(12):e1009190. doi: 10.1371/journal.pgen.1009190. eCollection 2020 Dec.
The genetic landscape of diseases associated with changes in bone mineral density (BMD), such as osteoporosis, is only partially understood. Here, we explored data from 3,823 mutant mouse strains for BMD, a measure that is frequently altered in a range of bone pathologies, including osteoporosis. A total of 200 genes were found to significantly affect BMD. This pool of BMD genes comprised 141 genes with previously unknown functions in bone biology and was complementary to pools derived from recent human studies. Nineteen of the 141 genes also caused skeletal abnormalities. Examination of the BMD genes in osteoclasts and osteoblasts underscored BMD pathways, including vesicle transport, in these cells and together with in silico bone turnover studies resulted in the prioritization of candidate genes for further investigation. Overall, the results add novel pathophysiological and molecular insight into bone health and disease.
与骨密度（BMD）变化相关疾病的遗传特征（如骨质疏松症）目前仅部分为人所知。在这里，我们研究了 3823 种突变小鼠品系的 BMD 数据，BMD 是一系列骨病理学中经常改变的指标，包括骨质疏松症。共有 200 个基因被发现显著影响 BMD。这些 BMD 基因包含 141 个以前在骨骼生物学中功能未知的基因，与最近的人类研究中得出的基因库互补。这 141 个基因中有 19 个也会导致骨骼异常。对破骨细胞和成骨细胞中的 BMD 基因进行检查，强调了这些细胞中的 BMD 通路，包括囊泡运输，与计算机骨骼周转率研究一起，对候选基因进行了进一步调查的优先级排序。总的来说，这些结果为骨骼健康和疾病提供了新的病理生理学和分子见解。
