Inhibition of RANKL-dependent cellular fusion in pre-osteoclasts by amiloride and a NHE10-specific monoclonal antibody

Yuichi Mine; Takahiro Shuto; Hiroki Nikawa; Toshihisa Kawai; Masaru Ohara; Kazuko Kawahara; Kouji Ohta; Toshio Kukita; Yoshihiro Terada; Seicho Makihira

doi:10.1002/cbin.10447

Inhibition of RANKL-dependent cellular fusion in pre-osteoclasts by amiloride and a NHE10-specific monoclonal antibody

Yuichi Mine, Takahiro Shuto, Hiroki Nikawa, Toshihisa Kawai, Masaru Ohara, Kazuko Kawahara, Kouji Ohta, Toshio Kukita, Yoshihiro Terada, Seicho Makihira

Research output: Contribution to journal › Article

3 Citations (Scopus)

Abstract

The functions of Na⁺/H⁺ exchangers (NHEs) during osteoclastic differentiation were investigated using the NHE inhibitor amiloride and a monoclonal antibody (MAb). Compared with sRANKL-stimulated control cells, amiloride decreased the number of large TRAP-positive osteoclast cells (OCs) with ≥10 nuclei and increased the number of small TRAP-positive OCs with ≤10 nuclei during sRANKL-dependent osteoclastic differentiation of RAW264.7 cells. NHE10 mRNA expression and OC differentiation markers were increased by sRANKL stimulation in dose- and time-dependent manners. NHEs 1-9 mRNA expression was not increased by sRANKL stimulation. Similar to amiloride, a rat anti-mouse NHE10 MAb (clone 6B11) decreased the number of large TRAP-positive OCs, but increased the number of small TRAP-positive OCs. These findings suggested that inhibition of NHEs by amiloride or an anti-NHE10 MAb prevented sRANKL-promoted cellular fusion. The anti-NHE10 MAb has the potential for use as an effective inhibitor of bone resorption for targeted bone disease therapy.

Original language	English
Pages (from-to)	696-709
Number of pages	14
Journal	Cell Biology International
Volume	39
Issue number	6
DOIs	https://doi.org/10.1002/cbin.10447
Publication status	Published - Jun 1 2015

All Science Journal Classification (ASJC) codes

Cell Biology

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Mine, Y., Shuto, T., Nikawa, H., Kawai, T., Ohara, M., Kawahara, K., Ohta, K., Kukita, T., Terada, Y., & Makihira, S. (2015). Inhibition of RANKL-dependent cellular fusion in pre-osteoclasts by amiloride and a NHE10-specific monoclonal antibody. Cell Biology International, 39(6), 696-709. https://doi.org/10.1002/cbin.10447

Inhibition of RANKL-dependent cellular fusion in pre-osteoclasts by amiloride and a NHE10-specific monoclonal antibody. / Mine, Yuichi; Shuto, Takahiro; Nikawa, Hiroki; Kawai, Toshihisa; Ohara, Masaru; Kawahara, Kazuko; Ohta, Kouji; Kukita, Toshio; Terada, Yoshihiro; Makihira, Seicho.

In: Cell Biology International, Vol. 39, No. 6, 01.06.2015, p. 696-709.

Research output: Contribution to journal › Article

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abstract = "The functions of Na+/H+ exchangers (NHEs) during osteoclastic differentiation were investigated using the NHE inhibitor amiloride and a monoclonal antibody (MAb). Compared with sRANKL-stimulated control cells, amiloride decreased the number of large TRAP-positive osteoclast cells (OCs) with ≥10 nuclei and increased the number of small TRAP-positive OCs with ≤10 nuclei during sRANKL-dependent osteoclastic differentiation of RAW264.7 cells. NHE10 mRNA expression and OC differentiation markers were increased by sRANKL stimulation in dose- and time-dependent manners. NHEs 1-9 mRNA expression was not increased by sRANKL stimulation. Similar to amiloride, a rat anti-mouse NHE10 MAb (clone 6B11) decreased the number of large TRAP-positive OCs, but increased the number of small TRAP-positive OCs. These findings suggested that inhibition of NHEs by amiloride or an anti-NHE10 MAb prevented sRANKL-promoted cellular fusion. The anti-NHE10 MAb has the potential for use as an effective inhibitor of bone resorption for targeted bone disease therapy.",

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