{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T23:35:16Z","timestamp":1792712116335,"version":"4.5.0"},"reference-count":32,"publisher":"National Academy of Sciences","issue":"7","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2001,3,27]]},"abstract":"<jats:p>\n                    Longitudinal bone growth is determined by endochondral ossification\n that occurs as chondrocytes in the cartilaginous growth plate undergo\n proliferation, hypertrophy, cell death, and osteoblastic replacement.\n The natriuretic peptide family consists of three structurally related\n endogenous ligands, atrial, brain, and C-type natriuretic\n peptides (ANP, BNP, and CNP), and is thought to be involved in a\n variety of homeostatic processes. To investigate the physiological\n significance of CNP\n                    <jats:italic>in vivo<\/jats:italic>\n                    , we generated mice with\n targeted disruption of CNP (\n                    <jats:italic>Nppc<\/jats:italic>\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mice).\n The\n                    <jats:italic>Nppc<\/jats:italic>\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mice show severe dwarfism as a\n result of impaired endochondral ossification. They are all viable\n perinatally, but less than half can survive during postnatal\n development. The skeletal phenotypes are histologically similar to\n those seen in patients with achondroplasia, the most common genetic\n form of human dwarfism. Targeted expression of CNP in the growth plate\n chondrocytes can rescue the skeletal defect of\n                    <jats:italic>Nppc<\/jats:italic>\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mice and allow their prolonged\n survival. This study demonstrates that CNP acts locally as a positive\n regulator of endochondral ossification\n                    <jats:italic>in vivo<\/jats:italic>\n                    and\n suggests its pathophysiological and therapeutic implication in some\n forms of skeletal dysplasia.\n                  <\/jats:p>","DOI":"10.1073\/pnas.071389098","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T10:37:36Z","timestamp":1027679856000},"page":"4016-4021","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":404,"title":["Dwarfism and early death in mice lacking C-type natriuretic peptide"],"prefix":"10.1073","volume":"98","author":[{"given":"Hideki","family":"Chusho","sequence":"first","affiliation":[{"name":"Department of Medicine and Clinical Science, Kyoto University\r Graduate School of Medicine, Kyoto 606-8507, Japan;\r Laboratory Animal Research Center, Institute of Medical\r Science, University of Tokyo, Tokyo 108-0071, Japan; and\r Suntory Institute for Biomedical Research, 1-1-1\r Wakayamadai, Shimamoto-cho, Mishima-gun, Osaka 618-0024, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naohisa","family":"Tamura","sequence":"additional","affiliation":[{"name":"Department of Medicine and Clinical Science, Kyoto University\r Graduate School of Medicine, Kyoto 606-8507, Japan;\r Laboratory Animal Research Center, Institute of Medical\r Science, University of Tokyo, Tokyo 108-0071, Japan; and\r Suntory Institute for Biomedical Research, 1-1-1\r Wakayamadai, Shimamoto-cho, Mishima-gun, Osaka 618-0024, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshihiro","family":"Ogawa","sequence":"additional","affiliation":[{"name":"Department of Medicine and Clinical Science, Kyoto University\r Graduate School of Medicine, Kyoto 606-8507, Japan;\r Laboratory Animal Research Center, Institute of Medical\r Science, University of Tokyo, Tokyo 108-0071, Japan; and\r Suntory Institute for Biomedical Research, 1-1-1\r Wakayamadai, Shimamoto-cho, Mishima-gun, Osaka 618-0024, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akihiro","family":"Yasoda","sequence":"additional","affiliation":[{"name":"Department of Medicine and Clinical Science, Kyoto University\r Graduate School of Medicine, Kyoto 606-8507, Japan;\r Laboratory Animal Research Center, Institute of Medical\r Science, University of Tokyo, Tokyo 108-0071, Japan; and\r Suntory Institute for Biomedical Research, 1-1-1\r Wakayamadai, Shimamoto-cho, Mishima-gun, Osaka 618-0024, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michio","family":"Suda","sequence":"additional","affiliation":[{"name":"Department of Medicine and Clinical Science, Kyoto University\r Graduate School of Medicine, Kyoto 606-8507, Japan;\r Laboratory Animal Research Center, Institute of Medical\r Science, University of Tokyo, Tokyo 108-0071, Japan; and\r Suntory Institute for Biomedical Research, 1-1-1\r Wakayamadai, Shimamoto-cho, Mishima-gun, Osaka 618-0024, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takashi","family":"Miyazawa","sequence":"additional","affiliation":[{"name":"Department of Medicine and Clinical Science, Kyoto University\r Graduate School of Medicine, Kyoto 606-8507, Japan;\r Laboratory Animal Research Center, Institute of Medical\r Science, University of Tokyo, Tokyo 108-0071, Japan; and\r Suntory Institute for Biomedical Research, 1-1-1\r Wakayamadai, Shimamoto-cho, Mishima-gun, Osaka 618-0024, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenji","family":"Nakamura","sequence":"additional","affiliation":[{"name":"Department of Medicine and Clinical Science, Kyoto University\r Graduate School of Medicine, Kyoto 606-8507, Japan;\r Laboratory Animal Research Center, Institute of Medical\r Science, University of Tokyo, Tokyo 108-0071, Japan; and\r Suntory Institute for Biomedical Research, 1-1-1\r Wakayamadai, Shimamoto-cho, Mishima-gun, Osaka 618-0024, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuki","family":"Nakao","sequence":"additional","affiliation":[{"name":"Department of Medicine and Clinical Science, Kyoto University\r Graduate School of Medicine, Kyoto 606-8507, Japan;\r Laboratory Animal Research Center, Institute of Medical\r Science, University of Tokyo, Tokyo 108-0071, Japan; and\r Suntory Institute for Biomedical Research, 1-1-1\r Wakayamadai, Shimamoto-cho, Mishima-gun, Osaka 618-0024, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatsuya","family":"Kurihara","sequence":"additional","affiliation":[{"name":"Department of Medicine and Clinical Science, Kyoto University\r Graduate School of Medicine, Kyoto 606-8507, Japan;\r Laboratory Animal Research Center, Institute of Medical\r Science, University of Tokyo, Tokyo 108-0071, Japan; and\r Suntory Institute for Biomedical Research, 1-1-1\r Wakayamadai, Shimamoto-cho, Mishima-gun, Osaka 618-0024, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasato","family":"Komatsu","sequence":"additional","affiliation":[{"name":"Department of Medicine and Clinical Science, Kyoto University\r Graduate School of Medicine, Kyoto 606-8507, Japan;\r Laboratory Animal Research Center, Institute of Medical\r Science, University of Tokyo, Tokyo 108-0071, Japan; and\r Suntory Institute for Biomedical Research, 1-1-1\r Wakayamadai, Shimamoto-cho, Mishima-gun, Osaka 618-0024, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroshi","family":"Itoh","sequence":"additional","affiliation":[{"name":"Department of Medicine and Clinical Science, Kyoto University\r Graduate School of Medicine, Kyoto 606-8507, Japan;\r Laboratory Animal Research Center, Institute of Medical\r Science, University of Tokyo, Tokyo 108-0071, Japan; and\r Suntory Institute for Biomedical Research, 1-1-1\r 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