Musculoskeletal Research Laboratory, Department of Orthopaedics & Traumatology, The Chinese University of Hong Kong, Hong Kong, China.
School of Biomedical Engineering, Sun Yat-sen University, Guangzhou, China; Musculoskeletal Research Laboratory, Department of Orthopaedics & Traumatology, The Chinese University of Hong Kong, Hong Kong, China.
Biomaterials. 2020 Apr;238:119828. doi: 10.1016/j.biomaterials.2020.119828. Epub 2020 Jan 31.
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.
镁（Mg）基生物金属因其可生物降解性和对组织再生的有益生物学效应而引起临床应用关注，尤其是在骨科领域，但相关临床疾病中的促合成代谢机制尚不清楚。本研究旨在探讨镁（Mg）和维生素 C（VC）补充剂预防类固醇相关骨坏死（SAON）的作用，采用大鼠实验模型进行研究。在 SAON 大鼠中，50mg/kg Mg、100mg/kg VC 或两者联合补充，或水对照，每日口服补充 2 或 6 周。通过组织学评估骨坏死。测量血清 Mg、VC 和骨转换标志物。通过 micro-CT 评估用于血管造影和小梁结构的微灌注样本。从每组分离原代骨髓细胞，以评估其在成骨细胞和破骨细胞形成中的潜力。在体外进行机制测试。组织学评估显示类固醇处理组存在 SAON 病变。Mg 和 VC 联合补充协同减少成骨细胞和破骨细胞数量的凋亡，并增加成骨细胞表面。VC 补充显著增加骨形成标志物 PINP，联合补充显著降低骨吸收标志物 CTX。Mg/VC/联合组骨髓中 TNFα 表达和氧化损伤减少。Mg 显著增加诱导 SAON 后 2 周时胫骨近端的血流灌注，并减少胫骨远端的漏出颗粒。VC 显著提高骨髓细胞的成骨细胞分化潜能，改善小梁结构。联合补充显著抑制骨髓细胞的破骨细胞分化潜能。体外研究显示 VC 具有促进成骨细胞分化的作用，Mg 具有抗炎和促进血管生成的作用，其潜在机制如下。Mg 和 VC 补充可协同缓解大鼠的 SAON，表明金属矿物质在预防 SAON 方面具有很大的转化潜力。
