OBJECTIVE: To investigate the effect of zoledronate (ZOL) on osteoclast differentiation and bone resorption under high glucose, and the regulation mechanism of p38 mitogen activated kinase (p38 MAPK) signaling pathway in this process. METHODS: RAW264.7 cells were divided into four groups: low group, high group, low+ZOL group and high+ZOL group after induced into osteoclasts. Cell proliferation activity was determined by MTT assay. The migration of RAW264.7 cells were examined Optical microscopy. Immunofluorescence microscopy was used to observe the cytoskeleton and sealing zones of osteoclasts. After adding group 5: high + ZOL + SB203580 group, trap staining was used to identify the number of positive osteoclasts in each group. The number and area of resorption lacunae were observed by SEM. The mRNA and protein expression of osteoclast related factors were detected by real-time PCR and Western blotting. RESULTS: The cells in the 5 groups showed similar proliferative activity. High glucose promoted the migration of RAW264.7 cells ( CONCLUSIONS High glucose inhibits osteoclast differentiation and bone resorption. ZOL inhibits osteoclast differentiation and bone resorption in high-glucose conditions by regulating p38 MAPK pathway, which can be a new pathway for ZOL to regulate diabetic osteoporosis.
Animals ; Bone Resorption ; Cell Differentiation ; Glucose ; MAP Kinase Signaling System ; Mice ; NFATC Transcription Factors ; Osteoclasts ; RANK Ligand ; Zoledronic Acid/pharmacology* ; p38 Mitogen-Activated Protein Kinases