Olstad Ole Kristoffer, Gautvik Vigdis Teig, LeBlanc Marissa, Kvernevik Karl Johnny, Utheim Tor Paaske, Runningen Anne, Wiig Håvard, Kirkegaard Camilla, Raastad Truls, Reppe Sjur, Gautvik Kaare Morten
Department of Medical Biochemistry, Oslo University Hospital, Oslo, Norway.
Unger-Vetlesen Institute, Lovisenberg Diaconal Hospital, Oslo, Norway.
Ther Adv Musculoskelet Dis. 2020 May 28;12:1759720X20929443. doi: 10.1177/1759720X20929443. eCollection 2020.
Clinical evidence suggests that body muscle mass is positively associated with bone mass, of significance for the elderly population at risk of osteoporosis (OP). Furthermore, muscle and bone interact mechanically and functionally, local interactions as well as remotely secreted components. Thus, it was of interest to compare muscle transcriptomes in postmenopausal OP and healthy women, and study effects of strength training on the muscle transcriptome, muscle stress proteins and bone mineral density (BMD).
Skeletal muscle histological and genetic properties were compared in postmenopausal healthy ( = 18) and OP ( = 17) women before and after heavy-load strength training for 13-15 weeks. The cohorts were of similar age and body mass index without interfering diseases, medication or difference in lifestyle factors. Muscle biopsies obtained before and after intervention were studied histologically, and stress proteins and transcriptomes analyzed.
The OP women showed distinct muscle transcription profiles when compared with healthy women and had higher levels of the stress proteins HSP70 and α-β-crystalline. A set of 12 muscle transcripts, including ACSS3, FZD4, GNAI1 and IGF1, were differentially expressed before and after intervention (false discovery rate ⩽0.10, ⩽0.001), and their corresponding bone transcripts were associated with BMD. Experimental data underline and describe the functionality of these genes in bone biology. OP women had 8% ( <0.01) higher proportion of type I fibres, but muscle fibre cross-sectional area did not differ. Muscle strength increased in both groups ( <0.01).
Postmenopausal healthy and OP women have distinct muscle transcriptomes [messenger ribonucleic acids (mRNAs) and microRNAs] that are modulated by strength training, translating into key protein alterations and muscle fibre changes. The function of common skeletal muscle and bone genes in postmenopausal OP is suggestive of a shared disease trait.
临床证据表明,身体肌肉质量与骨量呈正相关,这对有骨质疏松症(OP)风险的老年人群具有重要意义。此外,肌肉和骨骼在机械和功能上相互作用,包括局部相互作用以及远程分泌成分。因此,比较绝经后OP女性和健康女性的肌肉转录组,并研究力量训练对肌肉转录组、肌肉应激蛋白和骨矿物质密度(BMD)的影响具有重要意义。
对18名绝经后健康女性和17名OP女性进行了13 - 15周的重负荷力量训练,比较训练前后骨骼肌的组织学和遗传学特性。两组人群年龄和体重指数相似,无干扰性疾病、药物治疗或生活方式因素差异。对干预前后获取的肌肉活检样本进行组织学研究,并分析应激蛋白和转录组。
与健康女性相比,OP女性表现出明显不同的肌肉转录谱,且应激蛋白HSP70和α-β-晶状体蛋白水平更高。一组12种肌肉转录本,包括ACSS3、FZD4、GNAI1和IGF1,在干预前后差异表达(错误发现率⩽0.10,⩽0.001),且它们相应的骨转录本与BMD相关。实验数据强调并描述了这些基因在骨生物学中的功能。OP女性I型纤维比例高8%(<0.01),但肌纤维横截面积无差异。两组肌肉力量均增加(<0.01)。
绝经后健康女性和OP女性具有不同的肌肉转录组[信使核糖核酸(mRNA)和微小RNA],这些转录组受力量训练调节,转化为关键蛋白质改变和肌纤维变化。绝经后OP中常见骨骼肌和骨基因的功能提示存在共同的疾病特征。