{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T02:08:47Z","timestamp":1790820527849,"version":"4.1.0"},"reference-count":26,"publisher":"National Academy of Sciences","issue":"22","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[1998,10,27]]},"abstract":"<jats:p>\n                    During vertebrate limb development, growth plate chondrocytes undergo temporally and spatially coordinated differentiation that is necessary for proper morphogenesis. Parathyroid hormone-related peptide (PTHrP), its receptor, the PTH\/PTHrP receptor, and Indian hedgehog are implicated in the regulation of chondrocyte differentiation, but the specific cellular targets of these molecules and specific cellular interactions involved have not been defined. Here we generated chimeric mice containing both wild-type and PTH\/PTHrP receptor (\u2212\/\u2212) cells, and analyzed cell\u2013cell interactions in the growth plate\n                    <jats:italic>in vivo<\/jats:italic>\n                    . Abnormal differentiation of mutant cells shows that PTHrP directly signals to the PTH\/PTHrP receptor on proliferating chondrocytes to slow their differentiation. The presence of ectopically differentiated mutant chondrocytes activates the Indian hedgehog\/PTHrP axis and slows differentiation of wild-type chondrocytes. Moreover, abnormal chondrocyte differentiation affects mineralization of cartilaginous matrix in a non-cell autonomous fashion; matrix mineralization requires a critical mass of adjacent ectopic hypertrophic chondrocytes. Further, ectopic hypertrophic chondrocytes are associated with ectopic bone collars in adjacent perichondrium. Thus, the PTH\/PTHrP receptor directly controls the pace and synchrony of chondrocyte differentiation and thereby coordinates development of the growth plate and adjacent bone.\n                  <\/jats:p>","DOI":"10.1073\/pnas.95.22.13030","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T10:40:11Z","timestamp":1027680011000},"page":"13030-13035","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":222,"title":["The parathyroid hormone\/parathyroid hormone-related peptide receptor coordinates endochondral bone development by directly controlling chondrocyte differentiation"],"prefix":"10.1073","volume":"95","author":[{"given":"Ung-il","family":"Chung","sequence":"first","affiliation":[{"name":"Endocrine Unit, Massachusetts General Hospital, 50 Blossom Street, Wellman 501, Boston, MA 02114; Molecular Endocrinology, Max-Planck-Institut f\u00fcr Biochemie, Am Klopferspitz 18a, 82152 Martinsried bei M\u00fcnchen, Germany; and Cardiovascular Research Center, Massachusetts General Hospital East, Department of Medicine, Harvard Medical School, Charlestown, MA 02129"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beate","family":"Lanske","sequence":"additional","affiliation":[{"name":"Endocrine Unit, Massachusetts General Hospital, 50 Blossom Street, Wellman 501, Boston, MA 02114; Molecular Endocrinology, Max-Planck-Institut f\u00fcr Biochemie, Am Klopferspitz 18a, 82152 Martinsried bei M\u00fcnchen, Germany; and Cardiovascular Research Center, Massachusetts General Hospital East, Department of Medicine, Harvard Medical School, Charlestown, MA 02129"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaechoong","family":"Lee","sequence":"additional","affiliation":[{"name":"Endocrine Unit, Massachusetts General Hospital, 50 Blossom Street, Wellman 501, Boston, MA 02114; Molecular Endocrinology, Max-Planck-Institut f\u00fcr Biochemie, Am Klopferspitz 18a, 82152 Martinsried bei M\u00fcnchen, Germany; and Cardiovascular Research Center, Massachusetts General Hospital East, Department of Medicine, Harvard Medical School, Charlestown, MA 02129"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"En","family":"Li","sequence":"additional","affiliation":[{"name":"Endocrine Unit, Massachusetts General Hospital, 50 Blossom Street, Wellman 501, Boston, MA 02114; Molecular Endocrinology, Max-Planck-Institut f\u00fcr Biochemie, Am Klopferspitz 18a, 82152 Martinsried bei M\u00fcnchen, Germany; and Cardiovascular Research Center, Massachusetts General Hospital East, Department of Medicine, Harvard Medical School, Charlestown, MA 02129"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henry","family":"Kronenberg","sequence":"additional","affiliation":[{"name":"Endocrine Unit, Massachusetts General Hospital, 50 Blossom Street, Wellman 501, Boston, MA 02114; Molecular Endocrinology, Max-Planck-Institut f\u00fcr Biochemie, Am Klopferspitz 18a, 82152 Martinsried bei M\u00fcnchen, Germany; and Cardiovascular Research Center, Massachusetts General Hospital East, Department of Medicine, Harvard Medical School, Charlestown, MA 02129"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[1998,10,27]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(95)90487-5"},{"key":"e_1_3_3_2_2","first-page":"3","volume-title":"Principles of Bone Biology","author":"Marks S C","year":"1996","unstructured":"S C Marks, D C Hermey Principles of Bone Biology, eds J P Bilezikian, L G Raisz, G A Rodan (Academic, San Diego), pp. 3\u201314 (1996)."},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.93.19.10240"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.94.25.13689"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1101\/gad.8.3.277"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.126.6.1611"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1210\/endo.137.11.8895385"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.273.5275.663"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.273.5275.613"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(93)90626-2"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(93)90627-3"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(93)90628-4"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1006\/dbio.1995.0010"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1210\/endo.134.1.8275957"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1210\/endo.136.2.7835276"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1658941"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.94.8.3789"},{"key":"e_1_3_3_18_2","first-page":"71","volume-title":"Teratocarcinomas and Embryonic Stem Cells","author":"Robertson E J","year":"1987","unstructured":"E J Robertson Teratocarcinomas and Embryonic Stem Cells, ed E J Robertson (IRL, Oxford), pp. 71\u2013112 (1987)."},{"key":"e_1_3_3_19_2","first-page":"113","volume-title":"Teratocarcinomas and Embryonic Stem Cells","author":"Bradley A","year":"1987","unstructured":"A Bradley Teratocarcinomas and Embryonic Stem Cells, ed E J Robertson (IRL, Oxford), pp. 113\u2013152 (1987)."},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.129.5.1421"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1038\/384129a0"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1038\/384176a0"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1101\/gad.10.3.301"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.93.26.15233"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-5793(97)00014-8"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.1997.7156"}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.95.22.13030","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,13]],"date-time":"2022-04-13T16:09:12Z","timestamp":1649866152000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.95.22.13030"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1998,10,27]]},"references-count":26,"journal-issue":{"issue":"22","published-print":{"date-parts":[[1998,10,27]]}},"alternative-id":["10.1073\/pnas.95.22.13030"],"URL":"https:\/\/doi.org\/10.1073\/pnas.95.22.13030","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[1998,10,27]]},"assertion":[{"value":"1998-07-09","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"1998-10-27","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}