| Autor: |
Hideki, Tsumura, Miyuki, Shindo, Morihiro, Ito, Arisa, Igarashi, Kazue, Takeda, Kenji, Matsumoto, Takashi, Ohkura, Kenji, Miyado, Fumihiro, Sugiyama, Akihiro, Umezawa, Yasuhiko, Ito |
| Rok vydání: |
2021 |
| Předmět: |
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| Zdroj: |
Comp Med |
| ISSN: |
2769-819X |
| Popis: |
Slc1a5 (ASCT2) encodes a small neutral amino-acid exchanger and is the most well-studied glutamine transporter in cancer cells. To investigate the role of Slc1a5 in osteoclastogenesis, we developed Slc1a5-deficient mice by using a conventional gene-targeting approach. The Slc1a5(−/−) mice showed no obvious abnormalities in growth. Glutamine uptake was assessed in Slc1a5(+/+) and Slc1a5(−/−) bone marrow cells stimulated with RANKL. The rate of glutamine uptake in Slc1a5(−/−) bone marrow cells was reduced to 70% of that of cells from Slc1a5(+/+) bone marrow. To confirm the involvement of Slc1a5 in osteoclast formation, bone marrow cells derived from Slc1a5(+/+) or Slc1a5(−/−) mice were stimulated with RANKL and macrophage colony-stimulating factor and stained with tartrate-resistant acid phosphatase. The bone resorption activity and actin ring formation of stimulated cells were measured. The formation of multinucleated osteoclasts in bone marrow cells isolated from Slc1a5(−/−) mice was severely impaired compared with those from Slc1a5(+/+) mice. RANKL-induced expression of ERK, NFκB, p70S6K, and NFATc1 was suppressed in Slc1a5(−/−) osteoclasts. These results show that Slc1a5 plays an important role in osteoclast formation. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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