{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,3]],"date-time":"2026-05-03T12:37:55Z","timestamp":1777811875994,"version":"3.51.4"},"reference-count":34,"publisher":"SAGE Publications","issue":"3","license":[{"start":{"date-parts":[[2014,1,22]],"date-time":"2014-01-22T00:00:00Z","timestamp":1390348800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["J Dent Res"],"published-print":{"date-parts":[[2014,3]]},"abstract":"<jats:p>The temporomandibular joint (TMJ) functions as a load-bearing diarthrodial joint during mastication, and its continuous use and stress can lead to degeneration over age. Using senescence-accelerated (SAMP8) mice that develop early osteoarthritis-like changes in synovial joints at high frequency, we analyzed possible molecular mechanisms of TMJ degeneration and tested whether and how malocclusion may accelerate it. Condylar articular cartilage in young SAMP8 mice displayed early-onset osteoarthritic changes that included reductions in superficial\/chondroprogenitor cell number, proteoglycan\/collagen content, and Indian hedgehog ( Ihh)-expressing chondrocytes. Following malocclusion induced by tooth milling, the SAMP8 condyles became morphologically defective, displayed even lower proteoglycan levels, and underwent abnormal chondrocyte maturation compared with malocclusion-treated condyles in wild-type mice. Malocclusion also induced faster progression of pathologic changes with increasing age in SAMP8 condyles as indicated by decreased PCNA-positive proliferating chondroprogenitors and increased TUNEL-positive apoptotic cells. These changes were accompanied by steeper reductions in Ihh signaling and by expression of matrix metalloproteinase 13 at the chondro-osseous junction in SAMP8 articular cartilage. In sum, we show for the first time that precocious TMJ degeneration in SAMP8 mice is accompanied by\u2014and possibly attributable to\u2014altered Ihh signaling and that occlusal dysfunction accelerates progression toward degenerative TMJ disease in this model.<\/jats:p>","DOI":"10.1177\/0022034513519649","type":"journal-article","created":{"date-parts":[[2014,1,22]],"date-time":"2014-01-22T23:44:23Z","timestamp":1390434263000},"page":"281-287","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":27,"title":["TMJ Degeneration in SAMP8 Mice is Accompanied by Deranged Ihh Signaling"],"prefix":"10.1177","volume":"93","author":[{"given":"Y.","family":"Ishizuka","sequence":"first","affiliation":[{"name":"Department of Periodontology, Tokyo Dental College, Tokyo, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Y.","family":"Shibukawa","sequence":"additional","affiliation":[{"name":"Department of Clinical Oral Health Science, Tokyo Dental College, Tokyo, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M.","family":"Nagayama","sequence":"additional","affiliation":[{"name":"Department of Oral Pathology, Asahi University School of Dentistry, Gifu, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"R.","family":"Decker","sequence":"additional","affiliation":[{"name":"Division of Orthopaedic Surgery, The Children\u2019s Hospital of Philadelphia, Philadelphia, Pennsylvania, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"T.","family":"Kinumatsu","sequence":"additional","affiliation":[{"name":"Department of Periodontology, Tokyo Dental College, Tokyo, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A.","family":"Saito","sequence":"additional","affiliation":[{"name":"Department of Periodontology, Tokyo Dental College, Tokyo, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M.","family":"Pacifici","sequence":"additional","affiliation":[{"name":"Division of Orthopaedic Surgery, The Children\u2019s Hospital of Philadelphia, Philadelphia, Pennsylvania, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"E.","family":"Koyama","sequence":"additional","affiliation":[{"name":"Division of Orthopaedic Surgery, The Children\u2019s Hospital of Philadelphia, Philadelphia, Pennsylvania, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2014,1,22]]},"reference":[{"key":"bibr1-0022034513519649","doi-asserted-by":"publisher","DOI":"10.1177\/00220345880670091101"},{"key":"bibr2-0022034513519649","doi-asserted-by":"publisher","DOI":"10.1016\/j.joca.2008.05.021"},{"key":"bibr3-0022034513519649","first-page":"379","volume":"135","author":"Chen WH","year":"1989","journal-title":"Am J Pathol"},{"key":"bibr4-0022034513519649","doi-asserted-by":"publisher","DOI":"10.1038\/nature04117"},{"key":"bibr5-0022034513519649","doi-asserted-by":"publisher","DOI":"10.1177\/0022034511421930"},{"key":"bibr6-0022034513519649","doi-asserted-by":"publisher","DOI":"10.1177\/10454411950060030601"},{"key":"bibr7-0022034513519649","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.0010053"},{"key":"bibr8-0022034513519649","doi-asserted-by":"publisher","DOI":"10.1159\/000146153"},{"key":"bibr9-0022034513519649","doi-asserted-by":"publisher","DOI":"10.1016\/0047-6374(84)90168-4"},{"key":"bibr10-0022034513519649","doi-asserted-by":"publisher","DOI":"10.1016\/S1350-4533(02)00191-1"},{"key":"bibr11-0022034513519649","doi-asserted-by":"publisher","DOI":"10.1177\/00220345940730060401"},{"key":"bibr12-0022034513519649","doi-asserted-by":"publisher","DOI":"10.1177\/0022034511409407"},{"key":"bibr13-0022034513519649","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-0177(199611)207:3<344::AID-AJA11>3.0.CO;2-4"},{"key":"bibr14-0022034513519649","doi-asserted-by":"publisher","DOI":"10.1242\/dev.001586"},{"key":"bibr15-0022034513519649","doi-asserted-by":"publisher","DOI":"10.1126\/science.273.5275.663"},{"key":"bibr16-0022034513519649","doi-asserted-by":"publisher","DOI":"10.1038\/nm.2055"},{"key":"bibr17-0022034513519649","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0608449104"},{"key":"bibr18-0022034513519649","doi-asserted-by":"publisher","DOI":"10.1016\/0022-3913(80)90333-9"},{"key":"bibr19-0022034513519649","first-page":"611","volume":"18","author":"Moffett BC","year":"1969","journal-title":"Minerva Stomatol"},{"key":"bibr20-0022034513519649","doi-asserted-by":"publisher","DOI":"10.1177\/0022034510363078"},{"key":"bibr21-0022034513519649","doi-asserted-by":"publisher","DOI":"10.1177\/0022034513476302"},{"key":"bibr22-0022034513519649","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra0802472"},{"key":"bibr23-0022034513519649","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-7580.2006.00525.x"},{"key":"bibr24-0022034513519649","doi-asserted-by":"publisher","DOI":"10.1002\/dvdy.21036"},{"key":"bibr25-0022034513519649","doi-asserted-by":"publisher","DOI":"10.1101\/gad.13.16.2072"},{"key":"bibr26-0022034513519649","doi-asserted-by":"publisher","DOI":"10.1177\/0022034510397836"},{"key":"bibr27-0022034513519649","doi-asserted-by":"publisher","DOI":"10.1016\/0047-6374(81)90084-1"},{"key":"bibr28-0022034513519649","doi-asserted-by":"publisher","DOI":"10.1177\/154405910608500618"},{"key":"bibr29-0022034513519649","doi-asserted-by":"publisher","DOI":"10.1002\/j.0022-0337.2008.72.8.tb04569.x"},{"key":"bibr30-0022034513519649","doi-asserted-by":"publisher","DOI":"10.1177\/0022034509344387"},{"key":"bibr31-0022034513519649","doi-asserted-by":"publisher","DOI":"10.1177\/0022034510373766"},{"key":"bibr32-0022034513519649","doi-asserted-by":"publisher","DOI":"10.1177\/0022034512449170"},{"key":"bibr33-0022034513519649","first-page":"211","volume":"13","author":"Yokoyama T","year":"2001","journal-title":"J Jpan Soc"},{"key":"bibr34-0022034513519649","doi-asserted-by":"publisher","DOI":"10.1016\/j.ydbio.2006.07.028"}],"container-title":["Journal of Dental Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/0022034513519649","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.1177\/0022034513519649","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/0022034513519649","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T21:04:40Z","timestamp":1777496680000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1177\/0022034513519649"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,1,22]]},"references-count":34,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2014,3]]}},"alternative-id":["10.1177\/0022034513519649"],"URL":"https:\/\/doi.org\/10.1177\/0022034513519649","relation":{},"ISSN":["0022-0345","1544-0591"],"issn-type":[{"value":"0022-0345","type":"print"},{"value":"1544-0591","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,1,22]]}}}