Preventive effects of transcutaneous CO2 application on disuse osteoporosis and muscle atrophy in a rat hindlimb suspension model

IF 3.5 2区 医学 Q2 ENDOCRINOLOGY & METABOLISM
Bone Pub Date : 2024-09-18 DOI:10.1016/j.bone.2024.117262
Ryota Nishida , Tomoaki Fukui , Takahiro Niikura , Yohei Kumabe , Ryo Yoshikawa , Kyohei Takase , Yuya Yamamoto , Ryosuke Kuroda , Keisuke Oe
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引用次数: 0

Abstract

We previously demonstrated that transcutaneous CO2 application promotes muscle fiber-type switching, fracture healing, and osteogenesis by increasing blood flow and angiogenesis. Here, we aimed to investigate the preventive effects of transcutaneous CO2 application on disuse osteoporosis and muscle atrophy in a rat hindlimb suspension model. Eleven-week-old male Sprague-Dawley rats were divided into hindlimb suspension (HS), HS with transcutaneous CO2 application (HSCO2), and control groups. HSCO2 rats were administered transcutaneous 100 % CO2 gas in their bilateral hindlimbs, five times a week for 20 min. After 3 weeks, we harvested the gastrocnemius, femur, and tibia for assessment. Histological analysis revealed a significant decrease in the gastrocnemius myofiber cross-sectional area in HS rats compared to the control rats, whereas HSCO2 rats exhibited a significant increase compared to HS rats. Micro-computed tomography showed significant bone atrophy in the trabecular and cortical bones of the femur in HS rats compared to those of the control rats, whereas significant improvement was noted in HSCO2 rats. Histological analysis of the proximal tibia revealed more marrow adipose tissue in the HS rats than in the control rats. However, in the HSCO2 rats, fewer marrow adipose tissue and osteoclasts were observed. Moreover, HSCO2 rats had more osteoblasts and higher expression of peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) and vascular endothelial growth factor (VEGF) than the HS rats. The gastrocnemius and distal femur of HSCO2 rats also exhibited elevated PGC-1α and VEGF expression and upregulation of the myogenesis markers and osteogenesis markers compared to those of HS rats. This treatment effectively prevented disuse osteoporosis and muscle atrophy by promoting local angiogenesis and blood flow. PGC-1α is crucial for promoting this angiogenic pathway. Transcutaneous CO2 application may be a novel preventive procedure for disuse osteoporosis and muscle atrophy, complementing medication and rehabilitation.

Abstract Image

经皮二氧化碳应用对大鼠后肢悬吊模型中废用性骨质疏松症和肌肉萎缩的预防作用
我们曾证实,经皮施用二氧化碳可通过增加血流量和血管生成促进肌肉纤维类型转换、骨折愈合和骨生成。在此,我们旨在研究经皮施用二氧化碳对大鼠后肢悬吊模型中废用性骨质疏松症和肌肉萎缩的预防作用。将 11 周大的雄性 Sprague-Dawley 大鼠分为后肢悬吊组(HS)、经皮施用二氧化碳的 HS 组(HSCO2)和对照组。HSCO2 组大鼠的双侧后肢经皮通入 100% CO2 气体,每周 5 次,每次 20 分钟。3 周后,我们采集腓肠肌、股骨和胫骨进行评估。组织学分析表明,与对照组大鼠相比,HS大鼠的腓肠肌肌纤维横截面积明显减少,而与HS大鼠相比,HSCO2大鼠的腓肠肌肌纤维横截面积明显增加。显微计算机断层扫描显示,与对照组大鼠相比,HS 大鼠股骨的骨小梁和皮质骨明显萎缩,而 HSCO2 大鼠则有明显改善。胫骨近端组织学分析显示,HS 大鼠的骨髓脂肪组织多于对照组大鼠。然而,在 HSCO2 大鼠中观察到的骨髓脂肪组织和破骨细胞较少。此外,与 HS 大鼠相比,HSCO2 大鼠有更多的成骨细胞,过氧化物酶体增殖激活受体γ辅助激活剂 1-α(PGC-1α)和血管内皮生长因子(VEGF)的表达量也更高。与 HS 大鼠相比,HSCO2 大鼠的腓肠肌和股骨远端也显示出 PGC-1α 和血管内皮生长因子表达的升高,以及肌生成标志物和骨生成标志物的上调。这种治疗方法通过促进局部血管生成和血流,有效预防了废用性骨质疏松症和肌肉萎缩。PGC-1α是促进这一血管生成途径的关键。经皮施用二氧化碳可能是一种新型的废用性骨质疏松症和肌肉萎缩的预防方法,可作为药物治疗和康复治疗的补充。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Bone
Bone 医学-内分泌学与代谢
CiteScore
8.90
自引率
4.90%
发文量
264
审稿时长
30 days
期刊介绍: BONE is an interdisciplinary forum for the rapid publication of original articles and reviews on basic, translational, and clinical aspects of bone and mineral metabolism. The Journal also encourages submissions related to interactions of bone with other organ systems, including cartilage, endocrine, muscle, fat, neural, vascular, gastrointestinal, hematopoietic, and immune systems. Particular attention is placed on the application of experimental studies to clinical practice.
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