Magnesium (Mg)-based biometal attracts clinical applications due to its biodegradability and beneficial biological effects on tissue regeneration, especially in orthopaedics, yet the underlying anabolic mechanisms in relevant clinical disorders are lacking. The present study investigated the effect of magnesium (Mg) and vitamin C (VC) supplementation for preventing steroid-associated osteonecrosis (SAON) in a rat experimental model. In SAON rats, 50 mg/kg Mg, or 100 mg/kg VC, or combination, or water control was orally supplemented daily for 2 or 6 weeks respectively. Osteonecrosis was evaluated by histology. Serum Mg, VC, and bone turnover markers were measured. Microfil-perfused samples prepared for angiography and trabecular architecture were evaluated by micro-CT. Primary bone marrow cells were isolated from each group to evaluate their potentials in osteoblastogenesis and osteoclastogenesis. The mechanisms were tested in vitro. Histological evaluation showed SAON lesions in steroid treated groups. Mg and VC supplementation synergistically reduced the apoptosis of osteocytes and osteoclast number, and increased osteoblast surface. VC supplementation significantly increased the bone formation marker PINP, and the combination significantly decreased the bone resorption marker CTX. TNFα expression and oxidative injury were decreased in bone marrow in Mg/VC/combination group. Mg significantly increased the blood perfusion in proximal tibia and decreased the leakage particles in distal tibia 2 weeks after SAON induction. VC significantly elevated the osteoblast differentiation potential of marrow cells and improved the trabecular architecture. The combination supplementation significantly inhibited osteoclast differentiation potential of marrow cells. In vitro study showed promoting osteoblast differentiation effect of VC, and anti-inflammation and promoting angiogenesis effect of Mg with underlying mechanisms. Mg and VC supplementation could synergistically alleviate SAON in rats, indicating great translational potentials of metallic minerals for preventing SAON.

中文翻译：

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补充镁和维生素C可减轻大鼠模型中与类固醇相关的骨坏死。

基于镁（Mg）的生物金属由于其可生物降解性和对组织再生的有益生物学作用（特别是在骨科中）而吸引了临床应用，但仍缺乏相关临床疾病中潜在的合成代谢机制。本研究在大鼠实验模型中研究了补充镁（Mg）和维生素C（VC）预防类固醇相关性骨坏死（SAON）的作用。在SAON大鼠中，每天口服补充50 mg / kg Mg或100 mg / kg V​​C，或组合使用或用水控制，分别持续2周或6周。通过组织学评估骨坏死。测量血清Mg，VC和骨转换指标。通过micro-CT评价为血管造影和小梁结构准备的微丝灌注样品。从每组中分离出原代骨髓细胞，以评估其在成骨细胞和破骨细胞形成中的潜力。机制进行了体外测试。组织学评估显示类固醇治疗组SAON病变。补充镁和VC协同减少骨细胞凋亡和破骨细胞数量，并增加成骨细胞表面。VC补充剂显着增加了骨形成标记物PINP，而该组合显着降低了骨吸收标记物CTX。Mg / VC /联合用药组骨髓中TNFα的表达和氧化损伤降低。镁在SAON诱导后2周显着增加了胫骨近端的血液灌注，并减少了胫骨远端的渗漏颗粒。VC显着提高了骨髓细胞的成骨细胞分化潜能，并改善了小梁结构。联合补充显着抑制骨髓细胞的破骨细胞分化潜能。体外研究表明，其具有促进VC的成骨细胞分化作用，抗炎和增强Mg的血管生成作用的作用。补充镁和VC可以协同减轻大鼠的SAON，表明金属矿物质具有很大的翻译潜力，可预防SAON。