Augmentation of RANKL-induced osteoclast differentiation by Z-VAD-fmk, a pan-caspase inhibitor

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Osteoclast differentiation/activation is involved in orthodontic tooth movement at the compression sites of the alveolar bone. RANKL, a member of the TNF family, expressed on osteoblasts stimulates RANK expressed on preosteoclasts, resulting in differentiation of preosteoclasts into mature osteoclasts. Several members of the TNF family including TNF and Fas ligand can induce apoptosis via activation of caspases (especially caspase-3) in various cells. A recent report showed that caspase-3 was activated at the early stage (within 15 min) of RANKL-induced osteoclast differentiation and that RANKL-induced osteoclast differentiation was suppressed by caspase inhibitors. Here we investigated whether caspase-3 might be activated and play a role at the late stage of RANKL-induced osteoclast differentiation. A slight but significant increase of caspase-3 activity was detected in mouse monocytic RAW264 cells differentiated into mature osteoclasts by treatment with RANKL for 3 days. In contrast with the previous report, co-treatment with Z-VAD-fmk, a pan-caspase inhibitor, augmented RANKL-induced osteoclast differentiation in RAW264 cells. Augmentation of RANKL-induced osteoclast differentiation by Z-VAD-fmk was also detected in mouse bone marrow macrophages. These results suggest that activation of caspases (presumably caspase-3) may play an inhibitory role at the late stage of RANKL-induced osteoclast differentiation.
大阪歯科学会の論文
2013-04-00