2,6-di-O-methyl-β-cyclodextrin affects osteoclast survival via cholesterol depletion

抄録

Bone undergoes a continuous remodeling process in which it is resorbed by osteoclasts and simultaneously formed by osteoblasts. Although this remodeling is crucial for maintaining and repairing bone tissue, in osteoporosis, there is an imbalance in this process, resulting in excessive bone resorption and decreased bone density. Inhibition of osteoclast activity is important in the treatment of osteoporosis. We investigated whether methyl β-cyclodextrin (M-β-CD) and its derivatives (DM-β-CD and TM-β-CD), which can induce apoptosis in various cells, affect osteoclast survival. Mouse macrophage-like cells (RAW264.7) were cultured for three days in the presence of sRANKL and then stimulated with M-β-CDs (M-β-CD, DM-β-CD, or TM-β-CD) for one day. Subsequently, tartrate-resistant phosphatase (TRAP) staining was performed. Furthermore, low-density lipoprotein receptor (LDLR) expression was analyzed to confirm whether M-β-CDs induce cell death by depleting cholesterol from the cell membrane. The number of TRAP-positive multinucleated cells was reduced by TM-β-CD stimulation at a concentration of 1 mM. At a concentration of 5 mM, all M-β-CDs reduced the number of TRAP-positive multinucleated cells. In addition, DM-β-CD increased LDLR expression in RAW264.7 cells. These results suggest that DM-β-CD induces cholesterol depletion in osteoclasts, affecting their survival. (J Osaka Dent Univ 2024; 58: 95-99)