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Genetic backgrounds and redox conditions influence morphological characteristics and cell differentiation of osteoclasts in mice

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Abstract

Osteoclasts (OCLs) are multinucleated giant cells and are formed by the fusion of mononuclear progenitors of monocyte/macrophage lineage. It is known that macrophages derived from different genetic backgrounds exhibit quite distinct characteristics of immune responses. However, it is unknown whether OCLs from different genetic backgrounds show distinct characteristics. In this study, we showed that bone-marrow macrophages (BMMs) derived from C57BL/6, BALB/c and ddY mice exhibited considerably distinct morphological characteristics and cell differentiation into OCLs. The differentiation of BMMs into OCLs was comparatively quicker in the C57BL/6 and ddY mice, while that of BALB/c mice was rather slow. Morphologically, ddY OCLs showed a giant cell with a round shape, C57BL/6 OCLs were of a moderate size with many protrusions and BALB/c OCLs had the smallest size with fewer nuclei. The intracellular signaling of differentiation and expression levels of marker proteins of OCLs were different in the respective strains. Treatment of BMMs from the three different strains with the reducing agent N-acetylcysteine (NAC) or with the oxidation agent hydrogen peroxide (H2O2) induced changes in the shape and sizes of the cells and caused distinct patterns of cell differentiation and survival. Thus, genetic backgrounds and redox conditions regulate the morphological characteristics and cell differentiation of OCLs.

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Abbreviations

OCLs:

Osteoclasts

RANKL:

Receptor activator of NF-κB ligand

TRAP:

Tartrate-resistant acid phosphatase

BMMs:

Bone-marrow macrophages

NAC:

N-acetylcysteine

H2O2 :

Hydrogen peroxide

M-CSF:

Macrophage-colony-stimulating factor

NFATc1:

Nuclear factor of activated T cells cytoplasmic-1

DC-STAM:

Dendritic cell-specific transmembrane protein

OC-STAMP:

Osteoclast stimulatory transmembrane protein

MMP:

Matrix metalloproteinase

TRAF6:

TNF receptor associated factor-6

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Acknowledgments

This work was supported in part by grants-in-aid for Scientific Research from the Ministry of Education, Science and Culture of Japan (E.S, T.T).

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Authors and Affiliations

  1. Division of Oral Pathopharmacology, Nagasaki University Graduate School of Biomedical Sciences, Sakamoto 1-7-1, Nagasaki, 852-8588, Japan

    Shun Narahara, Haruna Matsushima, Eiko Sakai, Yutaka Fukuma, Kazuhisa Nishishita, Kuniaki Okamoto & Takayuki Tsukuba

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  1. Shun Narahara
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  2. Haruna Matsushima
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  3. Eiko Sakai
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  4. Yutaka Fukuma
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  5. Kazuhisa Nishishita
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  6. Kuniaki Okamoto
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  7. Takayuki Tsukuba
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Corresponding authors

Correspondence to Eiko Sakai or Takayuki Tsukuba.

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Shun Narahara and Haruna Matsushima contributed equally to this work.

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Narahara, S., Matsushima, H., Sakai, E. et al. Genetic backgrounds and redox conditions influence morphological characteristics and cell differentiation of osteoclasts in mice. Cell Tissue Res 348, 81–94 (2012). https://doi.org/10.1007/s00441-012-1325-8

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  • DOI: https://doi.org/10.1007/s00441-012-1325-8

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