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Open Access Research article

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

Hiroki Yokota12*, Kazunori Hamamura1, Andy Chen1, Todd R Dodge1, Nancy Tanjung1, Aysan Abedinpoor1 and Ping Zhang123*

Author Affiliations

1 Department of Biomedical Engineering, Indiana University-Purdue University Indianapolis, 723 West Michigan Street, SL220, Indianapolis, IN, 46202, USA

2 Department of Anatomy and Cell Biology, Indiana University School of Medicine, Indianapolis, IN, 46202, USA

3 School of Basic Medical Sciences, Tianjin Medical University, Tanjin, 300070, People’s Republic of China

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BMC Musculoskeletal Disorders 2013, 14:197  doi:10.1186/1471-2474-14-197

Published: 1 July 2013

Abstract

Background

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?

Methods

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.

Results

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.

Conclusions

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.

Keywords:
Osteoporosis; RANKL; Salubrinal; Osteoclasts; Osteoblasts