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Publication : Nuclear factor of activated T cells 2 is required for osteoclast differentiation and function in vitro but not in vivo.

First Author  Yu J Year  2018
Journal  J Cell Biochem Volume  119
Issue  11 Pages  9334-9345
PubMed ID  30010214 Mgi Jnum  J:289229
Mgi Id  MGI:6434694 Doi  10.1002/jcb.27212
Citation  Yu J, et al. (2018) Nuclear factor of activated T cells 2 is required for osteoclast differentiation and function in vitro but not in vivo. J Cell Biochem 119(11):9334-9345
abstractText  Nuclear factor of activated T cells (NFAT) c2 is important for the immune response and it compensates for NFATc1 for its effects on osteoclastogenesis, but its role in this process is not established. To study the function of NFATc2 in the skeleton, Nfatc2(loxP/loxP) mice, where the Nfact2 exon 2 is flanked by loxP sequences, were created and mated with mice expressing the Cre recombinase under the control of the Lyz2 promoter. Bone marrow-derived macrophage (BMM) from Lyz2(Cre/WT) ;Nfatc2(Delta/Delta) mice cultured in the presence of macrophage-colony stimulating factor and receptor activator of NF-kappaB ligand exhibited a decrease in the number and size of osteoclasts and a smaller sealing zone when compared to BMMs from Nfatc2(loxP/loxP) littermate controls. Bone resorption was decreased in osteoclasts from Lyz2(Cre/WT) ;Nfatc2(Delta/Delta) mice. This demonstrates that NFATc2 is necessary for optimal osteoclast maturation and function in vitro. Male and female Lyz2(Cre/WT) ;Nfatc2(Delta/Delta) mice did not exhibit an obvious skeletal phenotype by microcomputed tomography (muCT) at either 1 or 4 months of age when compared to Nfatc2(loxP/loxP) sex-matched littermates. Bone histomorphometry confirmed the muCT results, and conditional 4-month-old Lyz2(Cre/WT) ;Nfatc2(Delta/Delta) mice did not exhibit changes in parameters of bone histomorphometry. In conclusion, NFATc2 is necessary for optimal osteoclastogenesis in vitro, but its downregulation in the myeloid lineage has no consequences in skeletal remodeling in vivo.
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