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Dentin sialophophoprotein (DSPP) is a mandibular condylar cartilage ECM protein, and its deletion impacted cell proliferation and other extracellular matrix alterations of postnatal condylar cartilage. However, it remains unclear if long-term loss of function of DSPP leads to TMJ OA. The study aimed to test the hypothesis that long-term haploinsufficiency of DSPP causes TMJ OA.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Materials and methods<\/jats:title>\n                <jats:p>To determine whether <jats:italic>Dspp<\/jats:italic><jats:sup>+\/\u2013<\/jats:sup> mice exhibit TMJ OA but no severe tooth defects, mandibles of wild-type (WT), <jats:italic>Dspp<\/jats:italic><jats:sup>+\/\u2013<\/jats:sup>, and <jats:italic>Dspp<\/jats:italic> homozygous (<jats:italic>Dspp<\/jats:italic><jats:sup><jats:italic>\u2212\/\u2212<\/jats:italic><\/jats:sup>) mice were analyzed by Micro-computed tomography (micro-CT). To characterize the progression and possible mechanisms of osteoarthritic degeneration over time in <jats:italic>Dspp<\/jats:italic><jats:sup>+\/\u2013<\/jats:sup> mice over time, condyles of <jats:italic>Dspp<\/jats:italic><jats:sup>+\/\u2013<\/jats:sup> and WT mice were analyzed radiologically, histologically, and immunohistochemically.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>Micro-CT and histomorphometric analyses revealed that <jats:italic>Dspp<\/jats:italic><jats:sup>+\/\u2013<\/jats:sup> and <jats:italic>Dspp<\/jats:italic><jats:sup><jats:italic>\u2212\/\u2212<\/jats:italic><\/jats:sup> mice had significantly lower subchondral bone mass, bone volume fraction, bone mineral density, and trabecular thickness compared to WT mice at 12\u00a0months. Interestingly, in contrast to <jats:italic>Dspp<\/jats:italic><jats:sup><jats:italic>\u2212\/\u2212<\/jats:italic><\/jats:sup> mice which exhibited tooth loss, <jats:italic>Dspp<\/jats:italic><jats:sup>+\/\u2013<\/jats:sup> mice had minor tooth defects. RNA sequencing data showed that haplodeficency of DSPP affects the biological process of ossification and osteoclast differentiation. Additionally, histological analysis showed that <jats:italic>Dspp<\/jats:italic><jats:sup>+\/\u2013<\/jats:sup> mice had condylar cartilage fissures, reduced cartilage thickness, decreased articular cell numbers and severe subchondral bone cavities, and with signs that were exaggerated with age. Radiographic data showed an increase in subchondral osteoporosis up to 18\u00a0months and osteophyte formation at 21\u00a0months. Moreover, <jats:italic>Dspp<\/jats:italic><jats:sup>+\/\u2013<\/jats:sup> mice showed increased distribution of osteoclasts in the subchondral bone and increased expression of MMP2, IL-6, FN-1, and TLR4 in the mandibular condylar cartilage.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p><jats:italic>Dspp<\/jats:italic><jats:sup>+\/\u2013<\/jats:sup> mice exhibit TMJ OA in a time-dependent manner, with lesions in the mandibular condyle attributed to hypomineralization of subchondral bone and breakdown of the mandibular condylar cartilage, accompanied by upregulation of inflammatory markers.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s12903-024-04320-8","type":"journal-article","created":{"date-parts":[[2024,5,14]],"date-time":"2024-05-14T16:02:54Z","timestamp":1715702574000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Long-term haplodeficency of DSPP causes temporomandibular joint osteoarthritis in mice"],"prefix":"10.1186","volume":"24","author":[{"given":"Qilin","family":"Liu","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yitong","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Haibo","family":"Shi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Danwei","family":"Xiang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chunye","family":"Wu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lina","family":"Song","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ning","family":"Ma","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hongchen","family":"Sun","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2024,5,14]]},"reference":[{"issue":"11","key":"4320_CR1","doi-asserted-by":"publisher","first-page":"1331","DOI":"10.1177\/0022034511421930","volume":"90","author":"M Embree","year":"2011","unstructured":"Embree M, Ono M, Kilts T, Walker D, Langguth J, Mao J, Bi Y, Barth JL, Young M. 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Clin Oral Investig. 2019;23(1):303\u201313.","journal-title":"Clin Oral Investig"}],"container-title":["BMC Oral Health"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12903-024-04320-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12903-024-04320-8\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12903-024-04320-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,14]],"date-time":"2024-05-14T16:03:40Z","timestamp":1715702620000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmcoralhealth.biomedcentral.com\/articles\/10.1186\/s12903-024-04320-8"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,5,14]]},"references-count":40,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2024,12]]}},"alternative-id":["4320"],"URL":"https:\/\/doi.org\/10.1186\/s12903-024-04320-8","relation":{},"ISSN":["1472-6831"],"issn-type":[{"type":"electronic","value":"1472-6831"}],"subject":[],"published":{"date-parts":[[2024,5,14]]},"assertion":[{"value":"14 September 2023","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"2 May 2024","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"14 May 2024","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"All animal experiments were performed with the approval of the Animal Care and Use Committee at Jilin University. We confirm that all methods were carried out in accordance with relevant guidelines and regulations and we confirm that all methods are reported in accordance with ARRIVE guidelines 2.0 for the reporting of animal experiments.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"569"}}