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Pfn1 supports the locomotion of most adherent cells by assisting actin\u2010filament elongation, as has been shown in skeletal progenitor cells in our previous study. However, because Pfn1 has also been known to inhibit migration of certain cells, including T cells, by suppressing branched\u2010end elongation of actin filaments, we hypothesized that its roles in osteoclasts may be different from that of osteoblasts. By investigating the osteoclasts in culture, we first verified that <jats:italic>Pfn1\u2010<\/jats:italic>knockdown (KD) enhances bone resorption in preosteoclastic RAW264.7 cells, despite having a comparable number and size of osteoclasts. <jats:italic>Pfn1<\/jats:italic>\u2010KD in bone marrow cells showed similar results. Mechanistically, <jats:italic>Pfn1\u2010<\/jats:italic>KD osteoclasts appeared more mobile than in controls. In vivo, the osteoclast\u2010specific conditional <jats:italic>Pfn1<\/jats:italic>\u2010deficient mice (<jats:italic>Pfn1<\/jats:italic>\u2010cKO) by CathepsinK\u2010Cre driver demonstrated postnatal skeletal phenotype, including dwarfism, craniofacial deformities, and long\u2010bone metaphyseal osteolytic expansion, by 8 weeks of age. Metaphyseal and diaphyseal femurs were drastically expanded with suppressed trabecular bone mass as indicated by \u03bcCT analysis. Histologically, TRAP\u2010positive osteoclasts were increased at endosteal metaphysis to diaphysis of <jats:italic>Pfn1<\/jats:italic>\u2010cKO mice. The enhanced movement of <jats:italic>Pfn1<\/jats:italic>\u2010cKO osteoclasts in culture was associated with a slight increase in cell size and podosome belt length, as well as an increase in bone\u2010resorbing activity. Our study, for the first time, demonstrated that <jats:italic>Pfn1<\/jats:italic> has critical roles in inhibiting osteoclast motility and bone resorption, thereby contributing to essential roles in postnatal skeletal homeostasis. Our study also provides novel insight into understanding skeletal deformities in human disorders. \u00a9 2018 American Society for Bone and Mineral Research.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jbm4.10130","type":"journal-article","created":{"date-parts":[[2018,12,3]],"date-time":"2018-12-03T18:40:01Z","timestamp":1543862401000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Profilin 1 Negatively Regulates Osteoclast Migration in Postnatal Skeletal Growth, Remodeling, and Homeostasis in Mice"],"prefix":"10.1093","volume":"3","author":[{"given":"Jumpei","family":"Shirakawa","sequence":"first","affiliation":[{"name":"Department of Molecular Pharmacology Medical Research Institute Tokyo Medical and Dental University Tokyo Japan"},{"name":"Department of Oral Medicine and Stomatology School of Dental Medicine Tsurumi University Yokohama 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