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 | |
| Publication status | Published - Jun 1 2015 |
Fingerprint
All Science Journal Classification (ASJC) codes
- Cell Biology
Cite this
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
}
TY - JOUR
T1 - Inhibition of RANKL-dependent cellular fusion in pre-osteoclasts by amiloride and a NHE10-specific monoclonal antibody
AU - Mine, Yuichi
AU - Shuto, Takahiro
AU - Nikawa, Hiroki
AU - Kawai, Toshihisa
AU - Ohara, Masaru
AU - Kawahara, Kazuko
AU - Ohta, Kouji
AU - Kukita, Toshio
AU - Terada, Yoshihiro
AU - Makihira, Seicho
PY - 2015/6/1
Y1 - 2015/6/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84929506363&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84929506363&partnerID=8YFLogxK
U2 - 10.1002/cbin.10447
DO - 10.1002/cbin.10447
M3 - Article
C2 - 25612314
AN - SCOPUS:84929506363
VL - 39
SP - 696
EP - 709
JO - Cell Biology International
JF - Cell Biology International
SN - 1065-6995
IS - 6
ER -