Abstract
The transient receptor potential melastatin type 7 (TRPM7) channel is a widely expressed nonselective cation channel with fusion to the C-terminal alpha kinase domain and regarded as a key regulator of whole body Mg2+ homeostasis in mammals. However, the roles of TRPM7 during osteoclastogenesis in RAW264.7 cells and bone marrow-derived monocyte/macrophage precursor cells (BMMs) are not clear. In the present study, we investigate the roles of TRPM7 in osteoclastogenesis using methods of small interfering RNA (siRNA), RT-PCR, patch-clamp, and calcium imaging. RANKL (receptor activator of NF-?B ligand) stimulation did not affect the TRPM7 expression and TRPM7-mediated current was activated in HEK293, RAW264.7, and BMM cells by the regulation of Mg2+. Knock-down of TRPM7 by siTRPM7 reduced intracellular Ca2+ concentration ([Ca2+]i) increases by 0 mM [Mg2+]e in HEK293 cells and inhibited the generation of RANKL-induced Ca2+ oscillations in RAW264.7 cells. Finally, knock-down of TRPM7 suppressed RANKL-mediated osteoclastogenesis such as activation and translocation of NFATc1, formation of multinucleated cells, and the bone resorptive activity, sequentially. These results suggest that TRPM7 plays an essential role in the RANKL-induced [Ca2+]i oscillations that triggers the late stages of osteoclastogenesis.
| Original language | English |
|---|---|
| Pages (from-to) | 65-71 |
| Number of pages | 7 |
| Journal | Korean Journal of Physiology and Pharmacology |
| Volume | 17 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - 2013 Jan 1 |
Fingerprint
All Science Journal Classification (ASJC) codes
- Physiology
- Pharmacology
Cite this
}
TRPM7 is essential for rankl-induced osteoclastogenesis. / Yang, Yu Mi; Jung, Hwi Hoon; Lee, Sung Jun; Choi, Hyung Jun; Kim, Min Seuk; Shin, Dong Min.
In: Korean Journal of Physiology and Pharmacology, Vol. 17, No. 1, 01.01.2013, p. 65-71.Research output: Contribution to journal › Article
TY - JOUR
T1 - TRPM7 is essential for rankl-induced osteoclastogenesis
AU - Yang, Yu Mi
AU - Jung, Hwi Hoon
AU - Lee, Sung Jun
AU - Choi, Hyung Jun
AU - Kim, Min Seuk
AU - Shin, Dong Min
PY - 2013/1/1
Y1 - 2013/1/1
N2 - The transient receptor potential melastatin type 7 (TRPM7) channel is a widely expressed nonselective cation channel with fusion to the C-terminal alpha kinase domain and regarded as a key regulator of whole body Mg2+ homeostasis in mammals. However, the roles of TRPM7 during osteoclastogenesis in RAW264.7 cells and bone marrow-derived monocyte/macrophage precursor cells (BMMs) are not clear. In the present study, we investigate the roles of TRPM7 in osteoclastogenesis using methods of small interfering RNA (siRNA), RT-PCR, patch-clamp, and calcium imaging. RANKL (receptor activator of NF-?B ligand) stimulation did not affect the TRPM7 expression and TRPM7-mediated current was activated in HEK293, RAW264.7, and BMM cells by the regulation of Mg2+. Knock-down of TRPM7 by siTRPM7 reduced intracellular Ca2+ concentration ([Ca2+]i) increases by 0 mM [Mg2+]e in HEK293 cells and inhibited the generation of RANKL-induced Ca2+ oscillations in RAW264.7 cells. Finally, knock-down of TRPM7 suppressed RANKL-mediated osteoclastogenesis such as activation and translocation of NFATc1, formation of multinucleated cells, and the bone resorptive activity, sequentially. These results suggest that TRPM7 plays an essential role in the RANKL-induced [Ca2+]i oscillations that triggers the late stages of osteoclastogenesis.
AB - The transient receptor potential melastatin type 7 (TRPM7) channel is a widely expressed nonselective cation channel with fusion to the C-terminal alpha kinase domain and regarded as a key regulator of whole body Mg2+ homeostasis in mammals. However, the roles of TRPM7 during osteoclastogenesis in RAW264.7 cells and bone marrow-derived monocyte/macrophage precursor cells (BMMs) are not clear. In the present study, we investigate the roles of TRPM7 in osteoclastogenesis using methods of small interfering RNA (siRNA), RT-PCR, patch-clamp, and calcium imaging. RANKL (receptor activator of NF-?B ligand) stimulation did not affect the TRPM7 expression and TRPM7-mediated current was activated in HEK293, RAW264.7, and BMM cells by the regulation of Mg2+. Knock-down of TRPM7 by siTRPM7 reduced intracellular Ca2+ concentration ([Ca2+]i) increases by 0 mM [Mg2+]e in HEK293 cells and inhibited the generation of RANKL-induced Ca2+ oscillations in RAW264.7 cells. Finally, knock-down of TRPM7 suppressed RANKL-mediated osteoclastogenesis such as activation and translocation of NFATc1, formation of multinucleated cells, and the bone resorptive activity, sequentially. These results suggest that TRPM7 plays an essential role in the RANKL-induced [Ca2+]i oscillations that triggers the late stages of osteoclastogenesis.
UR - http://www.scopus.com/inward/record.url?scp=84876748951&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84876748951&partnerID=8YFLogxK
U2 - 10.4196/kjpp.2013.17.1.65
DO - 10.4196/kjpp.2013.17.1.65
M3 - Article
C2 - 23440520
AN - SCOPUS:84876748951
VL - 17
SP - 65
EP - 71
JO - Korean Journal of Physiology and Pharmacology
JF - Korean Journal of Physiology and Pharmacology
SN - 1226-4512
IS - 1
ER -