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Like amelogenin, Ambn is mainly associated with tooth development, especially biomineralization of enamel. Previous studies have shown reductions in the skeletal dimensions of Ambn\u2010deficient mice, suggesting that the protein also has effects on the differentiation of osteoblasts and\/or osteoclasts. However, the specific pathways used by Ambn to influence osteoclast differentiation have yet to be identified. In the present study, two cellular models, one based on bone marrow cells and another on RAW264.7 cells, were used to examine the effects of Ambn on receptor activator of nuclear factor kappa\u2010B ligand (RANKL)\u2010induced osteoclastogenesis. The results showed that Ambn suppresses osteoclast differentiation, cytoskeletal organization, and osteoclast function by the downregulation of the number of tartrate\u2010resistant acid phosphatase (TRAP)\u2010positive multinucleated osteoclasts, actin ring formation, and areas of pit resorption. The expression of the osteoclast\u2010specific genes TRAP, MMP9, cathepsin K, and osteoclast stimulatory transmembrane protein (OC\u2010STAMP) was abolished in the presence of Ambn, while that of nuclear factor of activated T cells cytoplasmic 1 (NFATc1), the master regulatory factor of osteoclastogenesis, was also attenuated by the downregulation of c\u2010Fos expression. In Ambn\u2010induced RAW264.7 cells, phosphorylation of cAMP\u2010response element\u2010binding protein (CREB), c\u2010Jun N\u2010terminal kinase (JNK), and p38 mitogen\u2010activated protein kinase (p38 MAPK), but not extracellular signal\u2010regulated kinase 1\/2 (ERK1\/2), was reduced. Calcium oscillation was also decreased in the presence of Ambn, suggesting its involvement in both RANKL\u2010induced osteoclastogenesis and costimulatory signaling. B\u2010lymphocyte\u2010induced maturation protein\u20101 (Blimp1), a transcriptional repressor of negative regulators of osteoclastogenesis, was also downregulated by Ambn, resulting in the elevated expression of v\u2010maf musculoaponeurotic fibrosarcoma oncogene family, protein B (MafB), B\u2010cell lymphoma 6 (Bcl6), and interferon regulatory factor\u20108 (Irf8). Taken together, these findings suggest that Ambn suppresses RANKL\u2010induced osteoclastogenesis by modulating the NFATc1 axis.<\/jats:p>","DOI":"10.1002\/jcp.27045","type":"journal-article","created":{"date-parts":[[2018,8,14]],"date-time":"2018-08-14T00:48:53Z","timestamp":1534207733000},"page":"1745-1757","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Ameloblastin attenuates RANKL\u2010mediated osteoclastogenesis by suppressing activation of nuclear factor of activated T\u2010cell cytoplasmic 1 (NFATc1)"],"prefix":"10.1002","volume":"234","author":[{"given":"Wichida","family":"Chaweewannakorn","sequence":"first","affiliation":[{"name":"Division of Infections and Molecular Biology, Department of Health Promotion Kyushu Dental University Fukuoka Japan"},{"name":"Division of Developmental Stomatognathic Function Science, Department of Health Promotion Kyushu Dental University Fukuoka 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