{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T13:26:26Z","timestamp":1791206786823,"version":"4.1.0"},"reference-count":29,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2010,10,4]],"date-time":"2010-10-04T00:00:00Z","timestamp":1286150400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal Orthopaedic Research"],"published-print":{"date-parts":[[2011,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Activating mutations in FGFR3 cause the most common forms of human dwarfism: achondroplasia and thanatophoric dysplasia. In mouse models of achondroplasia, recent studies have implicated the ERK MAPK pathway, a pathway activated by FGFR3, in creating reduced bone growth. Our recent studies have indicated that increased Fgfr3 and ERK MAPK signaling in chondrocytes also causes premature synchondrosis closure in the cranial base and vertebrae, accounting for the sometimes fatal stenosis of the foramen magnum and spinal canal in achondroplasia. Conversely, whether the decrease\u2014or inactivation\u2014of <jats:italic>ERK1<\/jats:italic> and <jats:italic>ERK2<\/jats:italic> promotes bone growth and delays synchondrosis closure remains to be investigated. In this study, we inactivated <jats:italic>ERK2<\/jats:italic> in the chondrocytes of <jats:italic>ERK1<\/jats:italic>\u2010null mice using the <jats:italic>Col2a1\u2010Cre<\/jats:italic> and <jats:italic>Col2a1\u2010CreER<\/jats:italic> transgenes. We found that the genetic inactivation of <jats:italic>ERK1<\/jats:italic> and <jats:italic>ERK2<\/jats:italic> in chondrocytes enhances the growth of cartilaginous skeletal elements. We also found that the postnatal inactivation of <jats:italic>ERK1<\/jats:italic> and <jats:italic>ERK2<\/jats:italic> in chondrocytes delays synchondrosis closure and enlarges the spinal canal. These observations make ERK1 and ERK2 an attractive target for the treatment of achondroplasia and other FGFR3\u2010related skeletal syndromes. \u00a9 2010 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 29:375\u2013379, 2011<\/jats:p>","DOI":"10.1002\/jor.21262","type":"journal-article","created":{"date-parts":[[2010,10,4]],"date-time":"2010-10-04T21:06:56Z","timestamp":1286226416000},"page":"375-379","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":41,"title":["Genetic inactivation of ERK1 and ERK2 in chondrocytes promotes bone growth and enlarges the spinal canal"],"prefix":"10.1002","volume":"29","author":[{"given":"Arjun","family":"Sebastian","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takehiko","family":"Matsushita","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aya","family":"Kawanami","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan","family":"Mackem","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gary E.","family":"Landreth","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shunichi","family":"Murakami","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2010,10,4]]},"reference":[{"key":"e_1_2_6_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/371252a0"},{"key":"e_1_2_6_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(94)90302-6"},{"key":"e_1_2_6_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng0595-11"},{"key":"e_1_2_6_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng0795-357"},{"key":"e_1_2_6_6_2","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1096-8628(19980707)78:3<274::AID-AJMG14>3.0.CO;2-C"},{"key":"e_1_2_6_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(07)61090-3"},{"key":"e_1_2_6_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng2073"},{"key":"e_1_2_6_9_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng1641"},{"key":"e_1_2_6_10_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1124642"},{"key":"e_1_2_6_11_2","doi-asserted-by":"crossref","first-page":"4977","DOI":"10.1242\/dev.125.24.4977","article-title":"Repression of hedgehog signaling and BMP4 expression in growth plate cartilage by fibroblast growth factor receptor 3","volume":"25","author":"Naski MC","year":"1998","journal-title":"Development"},{"key":"e_1_2_6_12_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.96.8.4455"},{"key":"e_1_2_6_13_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/9.2.249"},{"key":"e_1_2_6_14_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/9.11.1603"},{"key":"e_1_2_6_15_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng0496-390"},{"key":"e_1_2_6_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)81069-7"},{"key":"e_1_2_6_17_2","doi-asserted-by":"publisher","DOI":"10.1086\/508433"},{"key":"e_1_2_6_18_2","doi-asserted-by":"publisher","DOI":"10.1101\/gad.1179104"},{"key":"e_1_2_6_19_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm971"},{"key":"e_1_2_6_20_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.274.7.4293"},{"key":"e_1_2_6_21_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddn339"},{"key":"e_1_2_6_22_2","first-page":"454","article-title":"Mortality in achondroplasia","volume":"41","author":"Hecht JT","year":"1987","journal-title":"Am J Hum Genet"},{"key":"e_1_2_6_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-3476(84)81092-6"},{"key":"e_1_2_6_24_2","doi-asserted-by":"publisher","DOI":"10.1101\/lm.37001"},{"key":"e_1_2_6_25_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0679-08.2008"},{"key":"e_1_2_6_26_2","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1526-968X(200002)26:2<145::AID-GENE14>3.0.CO;2-C"},{"key":"e_1_2_6_27_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.01549-08"},{"key":"e_1_2_6_28_2","doi-asserted-by":"publisher","DOI":"10.1002\/dvdy.20892"},{"key":"e_1_2_6_29_2","doi-asserted-by":"publisher","DOI":"10.1002\/jor.1100090306"},{"key":"e_1_2_6_30_2","doi-asserted-by":"publisher","DOI":"10.1002\/jor.1100140613"}],"container-title":["Journal of Orthopaedic Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fjor.21262","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jor.21262","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,9]],"date-time":"2023-10-09T11:32:43Z","timestamp":1696851163000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/jor.21262"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2010,10,4]]},"references-count":29,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2011,3]]}},"alternative-id":["10.1002\/jor.21262"],"URL":"https:\/\/doi.org\/10.1002\/jor.21262","archive":["Portico"],"relation":{},"ISSN":["0736-0266","1554-527X"],"issn-type":[{"value":"0736-0266","type":"print"},{"value":"1554-527X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2010,10,4]]},"assertion":[{"value":"2010-05-25","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2010-08-17","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2010-10-04","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}