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Inhibition of RANKL‐dependent cellular fusion in pre‐osteoclasts by amiloride and a NHE10‐specific monoclonal antibody
Author(s) -
Mine Yuichi,
Shuto Takahiro,
Nikawa Hiroki,
Kawai Toshihisa,
Ohara Masaru,
Kawahara Kazuko,
Ohta Kouji,
Kukita Toshio,
Terada Yoshihiro,
Makihira Seicho
Publication year - 2015
Publication title -
cell biology international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.932
H-Index - 77
eISSN - 1095-8355
pISSN - 1065-6995
DOI - 10.1002/cbin.10447
Subject(s) - amiloride , monoclonal antibody , bone resorption , stimulation , rankl , microbiology and biotechnology , chemistry , antibody , medicine , biology , receptor , biochemistry , immunology , sodium , activator (genetics) , organic chemistry
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.