{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T18:58:52Z","timestamp":1787165932940,"version":"build-2736575974"},"reference-count":105,"publisher":"Wiley","issue":"S1","license":[{"start":{"date-parts":[[2025,4,19]],"date-time":"2025-04-19T00:00:00Z","timestamp":1745020800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2025,4,19]],"date-time":"2025-04-19T00:00:00Z","timestamp":1745020800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100000072","name":"National Institute of Dental and Craniofacial Research","doi-asserted-by":"publisher","award":["R35DE034348"],"award-info":[{"award-number":["R35DE034348"]}],"id":[{"id":"10.13039\/100000072","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000072","name":"National Institute of Dental and Craniofacial Research","doi-asserted-by":"publisher","award":["R01DE030630"],"award-info":[{"award-number":["R01DE030630"]}],"id":[{"id":"10.13039\/100000072","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000072","name":"National Institute of Dental and Craniofacial Research","doi-asserted-by":"publisher","award":["R01DE030416"],"award-info":[{"award-number":["R01DE030416"]}],"id":[{"id":"10.13039\/100000072","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Orthod Craniofacial Res"],"published-print":{"date-parts":[[2025,12]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>The mandibular condylar cartilage (MCC) is a dual\u2010function component of the temporomandibular joint (TMJ), acting as both articular cartilage for jaw movement and growth cartilage for vertical growth of the mandibular condyle. Parathyroid hormone\u2010related protein (PTHrP) plays a critical role in orchestrating chondrogenesis in the long bone, and its importance is also highlighted in both MCC development and TMJ function. Here, we discuss the role of PTHrP in the development, growth and diseases of the MCC. PTHrP is a key morphogen in the MCC that regulates chondrogenesis by promoting chondrocyte proliferation and preventing premature hypertrophic differentiation. Exclusively expressed in the superficial layer, PTHrP diffuses across the MCC and targets chondrocytes in deeper layers, regulating transcription factors such as RUNX2 and SOX9. PTHrP regulates chondrocyte differentiation through two main pathways: the PTHrP\u2010PTH1R signalling pathway, which suppresses hypertrophy and the PTHrP\u2010Ihh negative feedback loop, which balances proliferation and hypertrophy. In the postnatal murine MCC, PTHrP levels are high early on and decrease after the onset of mastication around P21. Altered mechanical environments, such as those therapeutically induced as mandibular advancement, increase PTHrP expression, promoting chondrocyte proliferation and delaying hypertrophy. PTHrP also plays a dual role in adult TMJ diseases, particularly in osteoarthritis (OA); PTHrP expression transiently increases during the early stages of TMJ\u2010OA to promote cell proliferation, but its eventual decrease contributes to the progression of the disease. This highlights the complex role of PTHrP in maintaining MCC homeostasis and its potential involvement in TMJ\u2010OA pathology. The MCC combines the characteristics of growth and articular cartilage and functions distinctively in three phases: development before occlusion, growth after the occlusion is established, and maintenance after the growth is complete. While PTHrP plays a multifaceted role in all phases, further research is needed to fully understand how it regulates MCC development, growth and diseases.<\/jats:p>","DOI":"10.1111\/ocr.12936","type":"journal-article","created":{"date-parts":[[2025,4,19]],"date-time":"2025-04-19T04:05:07Z","timestamp":1745035507000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Mandibular Condylar Cartilage in Development and Diseases: A\n                    <scp>PTHrP<\/scp>\n                    \u2010Centric View"],"prefix":"10.1111","volume":"28","author":[{"given":"Chiaki","family":"Tsutsumi\u2010Arai","sequence":"first","affiliation":[{"name":"University of Texas Health Science Center at Houston School of Dentistry  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amy","family":"Tran","sequence":"additional","affiliation":[{"name":"University of Texas Health Science Center at Houston School of Dentistry  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuki","family":"Arai","sequence":"additional","affiliation":[{"name":"University of Texas Health Science Center at Houston School of Dentistry  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wanida","family":"Ono","sequence":"additional","affiliation":[{"name":"University of Texas Health Science Center at Houston School of Dentistry  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3771-8230","authenticated-orcid":false,"given":"Noriaki","family":"Ono","sequence":"additional","affiliation":[{"name":"University of Texas Health Science Center at Houston School of Dentistry  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,4,19]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbiomech.2008.12.012"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1023\/b:abme.0000007786.37957.65"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jdsr.2013.07.004"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1097\/GOX.0000000000003285"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/0003-9969(95)00105-0"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1177\/0022034516668321"},{"key":"e_1_2_9_8_1","volume-title":"Chondroid Bone, Secondary Cartilage, and Metaplasia","author":"Beresford W. A.","year":"1981"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00429-004-0393-2"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1469-7580.1997.19140561.x"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40610-015-0019-x"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1177\/0022034515598135"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1177\/154405910508400802"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/pr.2015.163"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.3616618"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-018-0662-5"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.8.3.277"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1177\/00220345231208175"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1359\/jbmr.1999.14.11.1838"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0003-9969(97)00096-4"},{"key":"e_1_2_9_21_1","first-page":"1","article-title":"Detailed Staging of Inbred C57BL\/6 Mice Between Theiler's [1972] Stages 18 and 21 (11\u201013\u2009Days of Gestation) Based on Craniofacial Development","volume":"16","author":"Miyake T.","year":"1996","journal-title":"Journal of Craniofacial Genetics and Developmental Biology"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0003-9969(99)00068-0"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1002\/dvdy.21036"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms20246300"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.12.12.3852"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0945\u2010053x(99)00009\u20108"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1210\/endo.137.11.8895385"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.13.16.2072"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.95.22.13030"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cellsig.2009.02.012"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M006564200"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1534-5807(02)00218-6"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1177\/1074248417702976"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1210\/endrev\/bnab005"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a031237"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.00415-09"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2007.02.004"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2010.09.008"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.11\u2010183277"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.02258"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.040709"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yexcr.2004.05.025"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.273.5275.613"},{"key":"e_1_2_9_44_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms20236009"},{"key":"e_1_2_9_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bone.2020.115359"},{"key":"e_1_2_9_46_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.128.22.4523"},{"key":"e_1_2_9_47_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.129.12.2977"},{"key":"e_1_2_9_48_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21186665"},{"key":"e_1_2_9_49_1","doi-asserted-by":"publisher","DOI":"10.1006\/dbio.1995.0010"},{"key":"e_1_2_9_50_1","doi-asserted-by":"publisher","DOI":"10.1196\/annals.1346.002"},{"key":"e_1_2_9_51_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.127.3.543"},{"key":"e_1_2_9_52_1","doi-asserted-by":"publisher","DOI":"10.1006\/excr.2001.5161"},{"key":"e_1_2_9_53_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature01657"},{"key":"e_1_2_9_54_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.128.24.5099"},{"key":"e_1_2_9_55_1","doi-asserted-by":"publisher","DOI":"10.1177\/154405910408300312"},{"key":"e_1_2_9_56_1","doi-asserted-by":"publisher","DOI":"10.1177\/154405910308200811"},{"key":"e_1_2_9_57_1","doi-asserted-by":"publisher","DOI":"10.2741\/1851"},{"key":"e_1_2_9_58_1","doi-asserted-by":"publisher","DOI":"10.1177\/0022034510390810"},{"key":"e_1_2_9_59_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.archoralbio.2015.01.003"},{"key":"e_1_2_9_60_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00784\u2010020\u201003225\u20104"},{"key":"e_1_2_9_61_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.joms.2004.12.005"},{"key":"e_1_2_9_62_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.111092198"},{"key":"e_1_2_9_63_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.98.1.160"},{"key":"e_1_2_9_64_1","doi-asserted-by":"publisher","DOI":"10.1111\/joor.13597"},{"key":"e_1_2_9_65_1","doi-asserted-by":"publisher","DOI":"10.1111\/jopr.13203"},{"key":"e_1_2_9_66_1","doi-asserted-by":"publisher","DOI":"10.1016\/0003-9969(91)90075-6"},{"key":"e_1_2_9_67_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajodo.2014.05.028"},{"issue":"5","key":"e_1_2_9_68_1","first-page":"468","article-title":"Effects of Dietary Consistency on the Mandible of Rats at the Growth Stage: Computed X\u2010Ray Densitometric and Cephalometric Analysis","volume":"72","author":"Maki K.","year":"2002","journal-title":"Angle Orthodontist"},{"key":"e_1_2_9_69_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0889-5406(05)80027-7"},{"key":"e_1_2_9_70_1","doi-asserted-by":"publisher","DOI":"10.11607\/ofph.2094"},{"key":"e_1_2_9_71_1","doi-asserted-by":"publisher","DOI":"10.1093\/ejo\/26.1.1"},{"key":"e_1_2_9_72_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11914-015-0290-z"},{"key":"e_1_2_9_73_1","doi-asserted-by":"publisher","DOI":"10.1159\/000088791"},{"key":"e_1_2_9_74_1","doi-asserted-by":"publisher","DOI":"10.1210\/er.2002\u20100033"},{"key":"e_1_2_9_75_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-0032-1319782"},{"key":"e_1_2_9_76_1","doi-asserted-by":"publisher","DOI":"10.22203\/eCM.v029a09"},{"key":"e_1_2_9_77_1","doi-asserted-by":"publisher","DOI":"10.1007\/pl00010638"},{"key":"e_1_2_9_78_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0736\u20100266(00)00040\u20101"},{"key":"e_1_2_9_79_1","doi-asserted-by":"publisher","DOI":"10.1186\/ar3117"},{"key":"e_1_2_9_80_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41536\u2010022\u201000247\u20102"},{"key":"e_1_2_9_81_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00310258"},{"key":"e_1_2_9_82_1","doi-asserted-by":"publisher","DOI":"10.1002\/jor.1100120404"},{"key":"e_1_2_9_83_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bone.2007.07.020"},{"key":"e_1_2_9_84_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.22285"},{"key":"e_1_2_9_85_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.23985"},{"key":"e_1_2_9_86_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.332.7542.639"},{"key":"e_1_2_9_87_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.34535"},{"key":"e_1_2_9_88_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jot.2021.06.003"},{"key":"e_1_2_9_89_1","doi-asserted-by":"publisher","DOI":"10.1155\/2019\/3904923"},{"key":"e_1_2_9_90_1","doi-asserted-by":"publisher","DOI":"10.1002\/1529-0131(199812)41:12<2152::AID-ART10>3.0.CO;2-X"},{"key":"e_1_2_9_91_1","doi-asserted-by":"publisher","DOI":"10.1136\/ard.2003.008904"},{"key":"e_1_2_9_92_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.30515"},{"key":"e_1_2_9_93_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.joca.2016.12.024"},{"key":"e_1_2_9_94_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.24843"},{"key":"e_1_2_9_95_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.25969"},{"key":"e_1_2_9_96_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0106497"},{"key":"e_1_2_9_97_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11357-020-00160-w"},{"key":"e_1_2_9_98_1","doi-asserted-by":"publisher","DOI":"10.1177\/0022034514535807"},{"key":"e_1_2_9_99_1","doi-asserted-by":"publisher","DOI":"10.1016\/bs.ctdb.2015.07.008"},{"key":"e_1_2_9_100_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10439\u2010015\u20101320\u20109"},{"key":"e_1_2_9_101_1","doi-asserted-by":"publisher","DOI":"10.1177\/0022034515574770"},{"key":"e_1_2_9_102_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jds.2022.08.001"},{"key":"e_1_2_9_103_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.202300037RR"},{"key":"e_1_2_9_104_1","doi-asserted-by":"publisher","DOI":"10.1002\/jbmr.1835"},{"key":"e_1_2_9_105_1","doi-asserted-by":"publisher","DOI":"10.1177\/1947603519833146"},{"key":"e_1_2_9_106_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41368\u2010022\u201000189\u2010x"}],"container-title":["Orthodontics &amp; Craniofacial Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/ocr.12936","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/ocr.12936","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/ocr.12936","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,11]],"date-time":"2026-03-11T09:17:56Z","timestamp":1773220676000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/ocr.12936"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,4,19]]},"references-count":105,"journal-issue":{"issue":"S1","published-print":{"date-parts":[[2025,12]]}},"alternative-id":["10.1111\/ocr.12936"],"URL":"https:\/\/doi.org\/10.1111\/ocr.12936","archive":["Portico"],"relation":{},"ISSN":["1601-6335","1601-6343"],"issn-type":[{"value":"1601-6335","type":"print"},{"value":"1601-6343","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,4,19]]},"assertion":[{"value":"2024-12-25","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-04-12","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-04-19","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}