Journal
JOURNAL OF CELLULAR PHYSIOLOGY
Volume 235, Issue 11, Pages 8432-8445Publisher
WILEY
DOI: 10.1002/jcp.29687
Keywords
HOXC8; KDM1A; migration; osteo-; dentinogenic differentiation; stem cells from apical papilla (SCAPs)
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Funding
- National Natural Science Foundation of China [81670948, 81625005]
- Program for Hundred-Thousand-Ten thousand Talents in Beijing [2018A16]
- CAMS Innovation Fund for Medical Sciences [2019-I2M-5-031]
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Enhancing the functions of mesenchymal stem cells (MSCs) is considered a potential approach for promoting tissue regeneration. In the present study, we investigate the role of HOXC8 in regulating differentiation and migration by using stem cells of the apical papilla (SCAPs). Our results showed that overexpression of HOXC8 suppressed the osteo-/dentinogenic differentiation, as detected by measuring alkaline phosphatase activity, in vitro mineralization, and the expressions of dentin sialophosphoprotein, dentin matrix acidic phosphoprotein 1, bone sialoprotein, runt-related transcription factor 2, and osterix in SCAPs, and inhibited in vivo osteo-/dentinogenesis of SCAPs. In addition, knockdown of HOXC8 promoted the osteo-/dentinogenic differentiation potentials of SCAPs. Mechanically, HOXC8 enhanced KDM1A transcription by directly binding to its promoter. HOXC8 and KDM1A also inhibited the migration and chemotaxis abilities of SCAPs. To sum up, HOXC8 negatively regulated the osteo-/dentinogenic differentiation and migration abilities of SCAPs by directly enhancing KDM1A transcription and indicated that HOXC8 and KDM1A could serve as potential targets for enhancing dental MSC mediated tissue regeneration.
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