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Published on: May 4, 2018
Blockers of K+/Cl- transporter/channels diminish proliferation of osteoblastic cells
Masahiro Maki1, Hiroaki Miyazaki, Naomi Niisato
1Department of Orthopaedics, Graduate School of Medical Science, Kyoto Prefectural University of Medicine.
Abstract:
In the preset report, we studied if blockers of the K+/Cl- cotransporter, and Cl- and K+ channels modify the proliferation of MC3T3-E1 osteoblastic cells. A blocker of the K+/Cl- cotransporter, DIOA (100 and 500 microM), diminished the cell proliferation. NPPB (100 and 300 microM, a blocker of Cl- channel) and quinine (100 and 500 microM, a blocker of K+ channel) also suppressed the proliferation of MC3T3-E1 cells. These blockers of the K+/Cl- cotransporter/channels (DIOA, NPPB and quinine) would increase the intracellular Cl- concentration ([Cl-]i). On the other hand, our previous study (Biochem. Biophys. Res. Commun. 361, 1038-1043, 2007) reported that a decrease in [Cl-]i diminished the proliferation of MC3T3-E1 osteoblastic cells. Taken together, the observations indicate that both increases and decreases in [Cl-]i diminish the proliferation of MC3T3-E1 osteoblastic cells.
Insights
Blockers of ion channels, including the K+/Cl- cotransporter, inhibit osteoblastic cell proliferation. Both increases and decreases in intracellular chloride concentration ([Cl-]i) negatively impact MC3T3-E1 cell growth.
Area of Science:
- Cell Biology
- Biochemistry
- Physiology
Background:
- Osteoblastic cells are crucial for bone formation.
- Ion transport plays a role in cellular processes, including proliferation.
- The K+/Cl- cotransporter and associated channels are involved in cell function.
Purpose of the Study:
- To investigate the effect of K+/Cl- cotransporter and ion channel blockers on MC3T3-E1 osteoblastic cell proliferation.
- To understand the role of intracellular chloride concentration ([Cl-]i) in osteoblast proliferation.
Main Methods:
- Treatment of MC3T3-E1 cells with DIOA (K+/Cl- cotransporter blocker).
- Treatment of MC3T3-E1 cells with NPPB (Cl- channel blocker) and quinine (K+ channel blocker).
- Assessment of cell proliferation rates following inhibitor treatment.
Main Results:
- DIOA significantly diminished MC3T3-E1 cell proliferation.
- NPPB and quinine also suppressed MC3T3-E1 cell proliferation.
- These blockers increase intracellular chloride concentration ([Cl-]i).
Conclusions:
- Inhibition of the K+/Cl- cotransporter and associated ion channels reduces osteoblastic cell proliferation.
- Both elevated and reduced intracellular chloride concentrations ([Cl-]i) impair MC3T3-E1 cell proliferation.
- Ion homeostasis is critical for osteoblast proliferation and function.
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