Transcriptional Profiling of Muscle in Females with Distal Radius Fracture and Functional Sarcopenia

Jeong-Hyun Kang, Jeong-Hwa Baek, Jin Kwang Lee, Seok Woo Hong
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Abstract

Skeletal muscle and bone interact with each other via mechanical and biochemical ways. This study aimed to investigate the molecular mechanisms of interaction between muscle and bone and by analyzing the transcriptional profiles of total RNA from muscle tissue of females with distal radius fractures. A total 30 female participants (mean age 71.1 ± 8.9 years) with distal radius fractures were recruited. Participants were categorized into two groups; the NORM group consisted of participants with T score of the areal bone mineral density (aBMD) of the femoral neck higher than -1.0, handgrip strength greater than 18 kg, and gait speed faster than 1.0 m/sec (n = 10). Otherwise, participants with T score of the aBMD of the femoral neck equal or less than -1.0, handgrip strength lower than 18 kg, and gait speed slower than 1.0 m/sec (n = 20) were categorized into EXP group. Pronator quadratus muscle samples were obtained from all participants. Total RNA was extracted from frozen muscle samples and sequenced. The gene ontology analysis demonstrated that the potential interactions between attached muscle function and density of the associated bone would be linked with collagen biosynthetic activity, and maintenance of extracellular matrix structures. The analysis of the pathway, network, and protein class exhibited that integrin signaling, inflammatory reactions, matrix metalloproteinase (MMP) activity, and extracellular matrix protein structure had possible associations with the molecular background of muscle-bone interaction. Through integrin signaling, MMP activity, inflammatory reactions, and collagen biosynthesis, muscle and bone may mutually interact with one another.
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桡骨远端骨折和功能性肌少症女性肌肉转录谱分析
骨骼肌和骨骼通过机械和生化方式相互作用。本研究旨在通过分析桡骨远端骨折女性患者肌肉组织总 RNA 的转录谱,研究肌肉与骨骼之间相互作用的分子机制。本研究共招募了 30 名桡骨远端骨折的女性患者(平均年龄为 71.1 ± 8.9 岁)。参与者被分为两组:正常组包括股骨颈骨密度(aBMD)T值高于-1.0、手握力大于18公斤、步速快于1.0米/秒的参与者(n = 10)。否则,将股骨颈 aBMD 的 T 值等于或小于-1.0、手握力低于 18 千克、步速慢于 1.0 米/秒(n = 20)的参与者归入 EXP 组。从所有参与者身上采集膝上曲肌样本。从冷冻的肌肉样本中提取总 RNA 并进行测序。基因本体分析表明,附着肌肉功能和相关骨骼密度之间的潜在相互作用与胶原蛋白的生物合成活动和细胞外基质结构的维护有关。对通路、网络和蛋白质类别的分析表明,整合素信号转导、炎症反应、基质金属蛋白酶(MMP)活性和细胞外基质蛋白质结构可能与肌肉-骨骼相互作用的分子背景有关。通过整合素信号转导、MMP活性、炎症反应和胶原蛋白的生物合成,肌肉和骨骼可能相互影响。
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