Shen Yang, Wang Haoming, Xie Hongwei, Zhang Jiateng, Ma Qingliang, Wang Shiyu, Yuan Putao, Xue Hong, Hong Huaxing, Fan Shunwu, Xu Wenbin, Xie Ziang
Department of Orthopaedic Surgery, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Key Laboratory of Musculoskeletal System Degeneration and Regeneration Translational Research of Zhejiang Province, Hangzhou, China.
J Orthop Translat. 2024 May 21;46:53-64. doi: 10.1016/j.jot.2024.03.003. eCollection 2024 May.
Osteoporosis is one of the most common bone diseases in middle-aged and elderly populations worldwide. The development of new drugs to treat the disease is a key focus of research. Current treatments for osteoporosis are mainly directed at promoting osteoblasts and inhibiting osteoclasts. However, there is currently no ideal approach for osteoporosis treatment. l-arginine is a semi-essential amino acid involved in a number of cellular processes, including nitric production, protein biosynthesis, and immune responses. We previously reported that l-arginine-derived compounds can play a regulatory role in bone homeostasis.
To investigate the specific effect of l-arginine on bone homeostasis.
Mildly aged and ovariectomized mouse models were used to study the effects of l-arginine on osteogenesis and angiogenesis, assessed by micro-computed tomography and immunostaining of bone tissue. The effect of l-arginine on osteogenesis, angiogenesis, and adipogenesis was further studied in vitro using osteoblasts obtained from cranial cap bone, endothelial cells, and an adipogenic cell line. Specific methods to assess these processes included lipid staining, cell migration, tube-forming, and wound-healing assays. Protein and mRNA expression was determined for select biomarkers.
We found that l-arginine attenuated bone loss and promoted osteogenesis and angiogenesis. l-arginine increased the activity of vascular endothelial cells, whereas it inhibited adipogenesis in vitro. In addition, we found that l-arginine altered the expression of PINK1/Parkin and Bnip3 in the mitochondria of osteoblast-lineage and endothelial cells, thereby promoting mitophagy and protecting cells from ROS. Similarly, l-arginine treatment effectively ameliorated osteoporosis in an ovariectomized mouse model.
l-arginine promotes angio-osteogenesis, and inhibits adipogenesis, effects mediated by the PINK1/Parkin- and Bnip3-mediated mitophagy.
L-arginine supplementation may be an effective adjunct therapy in the treatment of osteoporosis.
骨质疏松症是全球中老年人群中最常见的骨病之一。开发治疗该疾病的新药是研究的重点。目前治疗骨质疏松症的方法主要是促进成骨细胞生成和抑制破骨细胞。然而，目前尚无理想的骨质疏松症治疗方法。L-精氨酸是一种半必需氨基酸，参与多种细胞过程，包括一氧化氮生成、蛋白质生物合成和免疫反应。我们之前报道过L-精氨酸衍生化合物可在骨稳态中发挥调节作用。
研究L-精氨酸对骨稳态的具体作用。
使用轻度老龄和卵巢切除小鼠模型研究L-精氨酸对成骨和血管生成的影响，通过微型计算机断层扫描和骨组织免疫染色进行评估。使用从颅骨帽骨获得的成骨细胞、内皮细胞和脂肪生成细胞系，在体外进一步研究L-精氨酸对成骨、血管生成和脂肪生成的影响。评估这些过程的具体方法包括脂质染色、细胞迁移、管形成和伤口愈合试验。测定选定生物标志物的蛋白质和mRNA表达。
我们发现L-精氨酸减轻了骨质流失，促进了成骨和血管生成。L-精氨酸增加了血管内皮细胞的活性，而在体外抑制了脂肪生成。此外，我们发现L-精氨酸改变了成骨细胞谱系和内皮细胞线粒体中PINK1/Parkin和Bnip3的表达，从而促进线粒体自噬并保护细胞免受活性氧的影响。同样，L-精氨酸治疗有效改善了卵巢切除小鼠模型中的骨质疏松症。
L-精氨酸促进血管生成和成骨，并抑制脂肪生成，这些作用由PINK1/Parkin和Bnip3介导的线粒体自噬介导。
补充L-精氨酸可能是治疗骨质疏松症的有效辅助疗法。
