Mechanical Strain Influences Preosteoclasts Apoptosis through Mitochondrial Pathway

Background: Osteoclasts, the key differentiated cells mainly responsible for bone resorption, are sensitive to mechanical strain. However, the effect of mechanical strain on osteoclasts apoptosis is poorly understood. Objectives: To investigate the effects of mechanical strain on pre-osteoclast apoptosis in vitro. Methods: After treatment with osteoclast-inductive medium, the pre-osteoclastic RAW264.7 cells were subjected to mechanical strains of physiological 2500 micro strain (μs) and pathologic 5000 μs respectively. Then the apoptosis was detected with Annexin V-FITC/PI binding assay and colorimetric assay of caspase-3 activity, mitochondrial membrane potential (Δψ_m) was assayed with flow cytometry, and apoptotic proteins were detected with western blots. Results: The mechanical strain of 2500 μs decreased pre-osteoclast apoptosis ratio, caspase-3 activity, elevated Δψm and the level of Bcl-2, down-regulated the level of caspase-3 and cytochrome C in cytoplasm. The pre-osteoclasts subjected to 5000 μs strain showed no evident difference compared to unstrained group. Additionally, pretreatment with cyclosporine A, an inhibitor of mitochondrial permeability transition pore (mPTP), elevated Δψ_m and lowered mechanical strain of 2500 μs reduced apoptosis ratio. Conclusion: Physiological mechanical strain of 2500 μs inhibited pre-osteoclast apoptosis, and the 5000 μs strain had no significant effects on apoptosis. The physiological strain influenced pre-osteoclast apoptosis through mPTP/ cytochrome C of the mitochondrial pathway.

並列關鍵字

Mechanical Strain ； Osteoclast ； Apoptosis ； Mitochondria ； Cytochrome C

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