{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T18:15:54Z","timestamp":1783620954523,"version":"3.55.0"},"reference-count":51,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2023,3,21]],"date-time":"2023-03-21T00:00:00Z","timestamp":1679356800000},"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 of Pineal Research"],"published-print":{"date-parts":[[2023,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Tooth development is a complex process that is tightly controlled by circadian rhythm. Melatonin (MT) is a major hormonal regulator of the circadian rhythm, and influences dentin formation and odontoblastic differentiation during tooth development; however, the underlying mechanism remains elusive. This study investigated how MT regulates odontoblastic differentiation, with a special focus on its regulation of mitochondrial dynamics. In rat dental papilla cells (DPCs), we found that MT promotes odontoblastic differentiation concurrently with enhanced mitochondrial fusion, while disruption of mitochondrial fusion by depleting optic atrophy 1 (OPA1) impairs MT\u2010mediated differentiation and mitochondrial respiratory functions. Through RNA sequencing, we discovered that MT significantly upregulated malic enzyme 2 (ME2), a mitochondrial NAD(P)<jats:sup>+<\/jats:sup>\u2010dependent enzyme, and identified ME2 as a critical MT downstream effector that orchestrates odontoblastic differentiation, mitochondrial fusion, and respiration functions. By detecting the spatiotemporal expression of ME2 in developing tooth germs, and using tooth germ reconstituted organoids, we also provided <jats:italic>in vivo<\/jats:italic> and <jats:italic>ex vivo<\/jats:italic> evidence that ME2 promotes dentin formation, indicating a possible involvement of ME2 in MT\u2010modulated tooth development. Collectively, our findings offer novel understandings regarding the molecular mechanism by which MT affects cell differentiation and organogenesis, meanwhile, the critical role of ME2 in MT\u2010regulated mitochondrial functions is also highlighted.<\/jats:p>","DOI":"10.1111\/jpi.12865","type":"journal-article","created":{"date-parts":[[2023,3,3]],"date-time":"2023-03-03T05:38:40Z","timestamp":1677821920000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Melatonin\u2010mediated malic enzyme 2 orchestrates mitochondrial fusion and respiratory functions to promote odontoblastic differentiation during tooth development"],"prefix":"10.1111","volume":"74","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7932-9922","authenticated-orcid":false,"given":"Fuping","family":"Zhang","sequence":"first","affiliation":[{"name":"Hospital of Stomatology Sun Yat\u2010sen University Guangzhou China"},{"name":"Guangdong Provincial 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