Effect of eldecalcitol on articular cartilage through the regulation of transcription factor Erg in a murine model of knee osteoarthritis

• Published in: Biochemical and biophysical research communications 2018-01, Vol.495 (1), p.179-184
• Main Authors: Yamamura, Kazumasa, Ohta, Yoichi, Mamoto, Kenji, Sugama, Ryo, Minoda, Yukihide, Nakamura, Hiroaki
• Format: Article
• Language: English
• Subjects: 60 APPLIED LIFE SCIENCES; Animals; Articular cartilage; BLOOD; Bone Density Conservation Agents - therapeutic use; BONE JOINTS; CARTILAGE; Cartilage, Articular - drug effects; Cartilage, Articular - metabolism; Cartilage, Articular - pathology; Cells, Cultured; Disease Models, Animal; Disease Progression; Eldecalcitol; Erg; Male; MESSENGER-RNA; MICE; Mice, Inbred C57BL; Oncogene Proteins - genetics; Osteoarthritis; Osteoarthritis, Knee - drug therapy; Osteoarthritis, Knee - genetics; Osteoarthritis, Knee - pathology; TRANSCRIPTION FACTORS; Transcriptional Regulator ERG - genetics; Up-Regulation - drug effects; VITAMIN D; Vitamin D - analogs & derivatives; Vitamin D - therapeutic use
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2017.10.155

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 D3 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 (10−8 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. •Eldecalcitol slowed the progression of experimental osteoarthritis in mice.•This effect was observed at 4 weeks, but not at 12 weeks.•Effects were associated with increased Erg levels.•Eldecalcitol-treated cultured chondrocytes also upregulated Erg mRNA.