Open AccessRelationships between Slc1a5 and Osteoclastogenesis
Author(s) -
Hideki Tsumura,
Miyuki Shindo,
Morihiro Ito,
Arisa Igarashi,
Kazue Takeda,
Kenji Matsumoto,
Takashi Ohkura,
Kenji Miyado,
Fumihiro Sugiyama,
Akihiro Umezawa,
Yasuhiko Ito
Publication year - 2021
Publication title -
comparative medicine
Language(s) - English
Resource type - Journals
eISSN - 2769-819X
pISSN - 1532-0820
DOI - 10.30802/aalas-cm-21-000012
Subject(s) - osteoclast , bone marrow , chemistry , glutamine , bone resorption , rankl , microbiology and biotechnology , biology , immunology , biochemistry , endocrinology , amino acid , gene , activator (genetics) , in vitro
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 Slc1a 5 -/- 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.