Yamamura Kazumasa, Ohta Yoichi, Mamoto Kenji, Sugama Ryo, Minoda Yukihide, Nakamura Hiroaki
Department of Orthopaedic Surgery, Osaka City University Graduate School of Medicine, 1-4-3, Asahimachi, Abeno-ku, Osaka, 545-8585, Japan.
Department of Orthopaedic Surgery, Osaka City University Graduate School of Medicine, 1-4-3, Asahimachi, Abeno-ku, Osaka, 545-8585, Japan.
Biochem Biophys Res Commun. 2018 Jan 1;495(1):179-184. doi: 10.1016/j.bbrc.2017.10.155. Epub 2017 Oct 31.
Clinical studies have reported an association between low blood levels of 25-hydroxyvitamin D and the progression of osteoarthritis (OA), but the mechanism and effects of vitamin D signaling on articular chondrocytes and cartilage remains unclear. The purpose of this study was to investigate the effects of vitamin D on articular cartilage degeneration using eldecalcitol (ED-71), which is an active vitamin D analog. Eight-week old male C57BL/6NCrSlc mice were subjected to experimental surgery to induce OA and local treatments with 10 μL ED-71 (0.5 μg/mL) were administered weekly. Four and 12 weeks after surgery, joints were evaluated using histological scoring systems. In addition, gene expression was analyzed in chondrocytes that were isolated from wildtype neonatal mice, cultured, and treated with ED-71 (10 M). Joints treated with ED-71 demonstrated slowed progression of OA at 4 weeks after surgery, but few effects were observed at 12 weeks after surgery. Ets-related gene (Erg) expression was upregulated in OA articular cartilage, and further increased by ED-71 treatment. In primary chondrocytes cultured with ED-71, the gene expression of Erg and lubricin/proteoglycan 4 significantly increased, as compared to that of cells cultured without ED-71. Local treatment with ED-71 reduced degenerative changes to the articular cartilage during the early phase of experimental OA. Regulation of Erg by ED-71 in articular cartilage could confer resistance to early osteoarthritic changes.
临床研究报告称，血液中25-羟基维生素D水平低与骨关节炎（OA）的进展之间存在关联，但维生素D信号通路对关节软骨细胞和软骨的作用机制仍不清楚。本研究的目的是使用活性维生素D类似物 eldecalcitol（ED-71）来研究维生素D对关节软骨退变的影响。8周龄雄性C57BL/6NCrSlc小鼠接受实验性手术以诱导OA，并每周局部给予10μL ED-71（0.5μg/mL）。术后4周和12周，使用组织学评分系统对关节进行评估。此外，对从野生型新生小鼠分离、培养并用ED-71（10μM）处理的软骨细胞进行基因表达分析。用ED-71处理的关节在术后4周时OA进展减缓，但在术后12周时观察到的影响较小。Ets相关基因（Erg）在OA关节软骨中的表达上调，并通过ED-71处理进一步增加。与未用ED-71培养的细胞相比，用ED-71培养的原代软骨细胞中，Erg和润滑素/蛋白聚糖4的基因表达显著增加。在实验性OA的早期阶段，局部用ED-71治疗可减少关节软骨的退行性变化。ED-71对关节软骨中Erg的调节可赋予对早期骨关节炎变化的抵抗力。
