Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, Japan.
Department of Orthopaedic Surgery, Hyogo Prefectural Nishinomiya Hospital, Japan.
Bone. 2024 Dec;189:117262. doi: 10.1016/j.bone.2024.117262. Epub 2024 Sep 18.
We previously demonstrated that transcutaneous CO 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 CO 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 CO application (HSCO), and control groups. HSCO rats were administered transcutaneous 100 % CO 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 HSCO 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 HSCO rats. Histological analysis of the proximal tibia revealed more marrow adipose tissue in the HS rats than in the control rats. However, in the HSCO rats, fewer marrow adipose tissue and osteoclasts were observed. Moreover, HSCO 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 HSCO 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 CO application may be a novel preventive procedure for disuse osteoporosis and muscle atrophy, complementing medication and rehabilitation.
我们之前的研究表明，经皮 CO 应用通过增加血流量和血管生成来促进肌肉纤维类型转换、骨折愈合和成骨。在这里，我们旨在研究经皮 CO 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。将 11 周龄雄性 Sprague-Dawley 大鼠分为后肢悬吊（HS）、后肢悬吊加经皮 CO 应用（HSCO）和对照组。HSCO 大鼠的双侧后肢接受 100% CO 气体经皮治疗，每周 5 次，每次 20 分钟。3 周后，采集比目鱼肌、股骨和胫骨进行评估。组织学分析显示，与对照组大鼠相比，HS 大鼠的比目鱼肌肌纤维横截面积显著减小，而 HSCO 大鼠则显著增加。微计算机断层扫描显示，与对照组大鼠相比，HS 大鼠的股骨小梁和皮质骨均出现明显的骨萎缩，而 HSCO 大鼠则有明显改善。对胫骨近端的组织学分析显示，HS 大鼠的骨髓脂肪组织多于对照组大鼠。然而，在 HSCO 大鼠中，骨髓脂肪组织和破骨细胞较少。此外，HSCO 大鼠的成骨细胞较多，过氧化物酶体增殖物激活受体γ共激活因子 1-α（PGC-1α）和血管内皮生长因子（VEGF）的表达较高。与 HS 大鼠相比，HSCO 大鼠的比目鱼肌和远端股骨也表现出更高的 PGC-1α 和 VEGF 表达，以及成肌标志物和成骨标志物的上调。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 对促进这种血管生成途径至关重要。经皮 CO 应用可能是一种预防废用性骨质疏松症和肌肉萎缩的新方法，可与药物治疗和康复治疗相辅相成。
