Effects of salubrinal on development of osteoclasts and osteoblasts from bone marrow-derived cells

• Published in: BMC musculoskeletal disorders Vol. 14; no. 1; p. 197
• Main Authors: Yokota, Hiroki, Hamamura, Kazunori, Chen, Andy, Dodge, Todd R, Tanjung, Nancy, Abedinpoor, Aysan, Zhang, Ping
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 01.07.2013; BioMed Central
• Subjects: Animals; Bone density; Bone Density Conservation Agents - pharmacology; Bone marrow; Bone Marrow Cells - drug effects; Cell Adhesion - drug effects; Cell Movement - drug effects; Cell Survival - drug effects; Cells, Cultured; Cinnamates - pharmacology; Disease Models, Animal; Dose-Response Relationship, Drug; Drug therapy; Female; Health aspects; Medical research; Mice; Mice, Inbred C57BL; Musculoskeletal diseases; Osteoblasts; Osteoblasts - drug effects; Osteoblasts - pathology; Osteoclasts - drug effects; Osteoclasts - pathology; Osteoporosis; Osteoporosis - drug therapy; Physiological aspects; Stem cells; Stem Cells - drug effects; T cells; Thiourea - analogs & derivatives; Thiourea - pharmacology; United States; China; United States > US; Indianapolis Indiana
• ISSN: 1471-2474; 1471-2474
• DOI: 10.1186/1471-2474-14-197

Osteoporosis is a skeletal disease leading to an increased risk of bone fracture. Using a mouse osteoporosis model induced by administration of a receptor activator of nuclear factor kappa-B ligand (RANKL), salubrinal was recently reported as a potential therapeutic agent. To evaluate the role of salubrinal in cellular fates as well as migratory and adhesive functions of osteoclast/osteoblast precursors, we examined the development of primary bone marrow-derived cells in the presence and absence of salubrinal. We addressed a question: are salubrinal's actions more potent to the cells isolated from the osteoporotic mice than those isolated from the control mice? Using the RANKL-injected and control mice, bone marrow-derived cells were harvested. Osteoclastogenesis was induced by macrophage-colony stimulating factor and RANKL, while osteoblastogenesis was driven by dexamethasone, ascorbic acid, and β-glycerophosphate. The results revealed that salubrinal suppressed the numbers of colony forming-unit (CFU)-granulocyte/macrophages and CFU-macrophages, as well as formation of mature osteoclasts in a dosage-dependent manner. Salubrinal also suppressed migration and adhesion of pre-osteoclasts and increased the number of CFU-osteoblasts. Salubrinal was more effective in exerting its effects in the cells isolated from the RANKL-injected mice than the control. Consistent with cellular fates and functions, salubrinal reduced the expression of nuclear factor of activated T cells c1 (NFATc1) as well as tartrate-resistant acid phosphatase. The results support the notion that salubrinal exhibits significant inhibition of osteoclastogenesis as well as stimulation of osteoblastogenesis in bone marrow-derived cells, and its efficacy is enhanced in the cells harvested from the osteoporotic bone samples.