An inhibitory role for caspase-3 at the late stage of RANKL-induced osteoclast differentiation in RAW264 cells and mouse bone marrow macrophages

• Published in: Cell biology international Vol. 38; no. 6; pp. 723 - 728
• Main Authors: Katao, Yuko, Shishido, Mika, Inami, Kaoru, Matsumoto, Naoyuki, Sawai, Hirofumi
• Format: Journal Article
• Language: English
• Published: England Blackwell Publishing Ltd 01.06.2014; Wiley Subscription Services, Inc
• Subjects: Alveolar Process - metabolism; Animals; Apoptosis; Aspartic Acid - analogs & derivatives; Aspartic Acid - pharmacology; Bone marrow; Bone Marrow Cells - metabolism; Caspase 3 - metabolism; caspase-3; Cell Differentiation; Cell Line; Cell Survival; Cysteine Proteinase Inhibitors - pharmacology; Macrophages - metabolism; Mice; Oligopeptides - pharmacology; osteoclastogenesis; Osteoclasts - metabolism; RANK Ligand - pharmacology; RANKL; Rodents; Tooth Movement Techniques; Z-Asp-CH2-DCB; Z-DEVD-fmk; RANKL; Z-Asp-CH2-DCB; osteoclastogenesis; Z-DEVD-fmk; caspase-3
• ISSN: 1065-6995; 1095-8355
• DOI: 10.1002/cbin.10263

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 in osteoblasts, binds to RANK, a member of the TNF receptor family expressed on preosteoclasts, resulting in differentiation of preosteoclasts into mature osteoclasts. Several members of the TNF family, such as TNF and Fas ligand, can induce apoptosis by activation of caspase‐3. We have investigated whether caspase‐3 be involved in the late stage of RANKL‐induced osteoclast differentiation. Increased active caspase‐3 was found in mouse monocytic RAW264 cells differentiated into mature osteoclasts by treatment with RANKL for 3 days. Co‐treatment with Z‐Asp‐CH2‐DCB, a caspase‐3‐specific inhibitor, augmented RANKL‐induced osteoclast differentiation in RAW264 cells, also seen in mouse bone marrow macrophages. This suggests that activation of caspase‐3 may play an inhibitory role at the late stage of RANKL‐induced osteoclast differentiation.