LmnaG609G/G609G早衰症小鼠模型中骨基质矿化正常但生长板形态改变

IF 7 2区 医学 Q1 GERIATRICS & GERONTOLOGY
Stéphane Blouin, Markus A Hartmann, Nadja Fratzl-Zelman, Phaedra Messmer, Daniel Whisenant, Michael R Erdos, Francis S Collins, Maria Eriksson, Charlotte Strandgren, Wayne A Cabral, Thomas Dechat
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引用次数: 0

摘要

哈奇森-吉尔福德早衰综合征(HGPS)是一种罕见的遗传病,由编码 A 型片层蛋白的基因 LMNA 突变引起,导致早衰和寿命严重缩短。HGPS 的特征是生长缺陷、皮下脂肪和肌肉问题、皮肤皱纹、脱发和动脉粥样硬化。患者还会出现骨表型,骨矿物质密度降低、骨溶解和长骨明显脱钙。为了进一步阐明 HGPS 的组织变化,我们对 LmnaG609G/G609G 早老症小鼠模型的骨矿化进行了鉴定。我们使用定量反向散射电子成像技术分析了8周龄小鼠的股骨和15周龄小鼠的肱骨,以评估骨矿化密度分布、骨细胞裂隙切片和骨组织形态结构。组织切片用Giemsa和Goldner三色染色进行组织学评估。Lmna+/+和LmnaG609G/G609G小鼠的骨组织在3个不同的骨部位和特定的组织年龄具有相似的矿物质含量。骨细胞空洞的特征没有统计学差异,但在两个动物年龄段的 LmnaG609G/G609G 中发现了更多的空洞。骨组织形态计量学和组织学显示,原发性(8W:-23%,p=0.001;15W:-38%,p=0.002)和继发性海绵体中单位组织体积的骨量减少(8W:-36%,p=0.001;15W:-49%,ns),以及生长板发育不良,与对照组相比,LmnaG609G/G609G 小鼠的未矿化静止区和增殖区更薄(8W:-18%,p=0.006;15W:-25%,p=0.001)。总体而言,LmnaG609G/G609G 小鼠出现软骨发育不良,骨小梁体积减少。多个组织部位和年龄的矿物质含量结果表明,骨发育不良是骨形成受损而骨周转正常的结果。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Normal Bone Matrix Mineralization but Altered Growth Plate Morphology in the LmnaG609G/G609G Mouse Model of Progeria.

Hutchison-Gilford progeria syndrome (HGPS) is a rare genetic disease caused by a mutation in LMNA, the gene encoding A-type lamins, leading to premature aging with severely reduced life span. HGPS is characterized by growth deficiency, subcutaneous fat and muscle issue, wrinkled skin, alopecia, and atherosclerosis. Patients also develop a bone phenotype with reduced bone mineral density, osteolysis and striking demineralization of long bones. To further clarify the tissue modifications in HGPS, we characterized bone mineralization in the LmnaG609G/G609G progeria mouse model. Femurs from 8-week-old mice and humeri from 15-week-old mice were analyzed using quantitative backscattered electron imaging to assess bone mineralization density distribution, osteocyte lacunae sections and structural bone histomorphometry. Tissue sections were stained with Giemsa and Goldner trichrome for histologic evaluation. Bone tissue from Lmna+/+ and LmnaG609G/G609G mice had similar mineral content at 3 different bone sites with specific tissue ages. The osteocyte lacunae features were not statistically different, but more empty lacunae were found in LmnaG609G/G609G at both animal ages. Bone histomorphometry and histology demonstrated decreased bone volume per tissue volume in primary (8W: -23%, p=0.001; 15W: -38%, p=0.002) and secondary spongiosa (8W: -36%, p=0.001; 15W: -49 %, ns), as well as growth plate dysplasia with thinner unmineralized resting and proliferative zones in the LmnaG609G/G609G mice versus controls (8W: -18%, p=0.006; 15W: -25%, p=0.001). Overall, the LmnaG609G/G609G mouse develops chondrodysplasia with reduced trabecular bone volume. Mineral content findings at several tissue sites and ages suggest that bone dysplasia results from impaired bone formation with normal bone turnover.

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来源期刊
Aging and Disease
Aging and Disease GERIATRICS & GERONTOLOGY-
CiteScore
14.60
自引率
2.70%
发文量
138
审稿时长
10 weeks
期刊介绍: Aging & Disease (A&D) is an open-access online journal dedicated to publishing groundbreaking research on the biology of aging, the pathophysiology of age-related diseases, and innovative therapies for conditions affecting the elderly. The scope encompasses various diseases such as Stroke, Alzheimer's disease, Parkinson’s disease, Epilepsy, Dementia, Depression, Cardiovascular Disease, Cancer, Arthritis, Cataract, Osteoporosis, Diabetes, and Hypertension. The journal welcomes studies involving animal models as well as human tissues or cells.
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