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- Title
GREM1 Negatively Regulates Osteo-/Dentinogenic Differentiation of Dental Pulp Stem Cells via Association with YWHAH.
- Authors
Shu DIAO; Xiao HAN; Wei Long YE; Chen ZHANG; Dong Mei YANG; Zhi Peng FAN; Song Lin WANG
- Abstract
Objective: To investigate the biological regulatory function of Gremlin1 (GREM1) and tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein eta (YWHAH) in dental pulp stem cells (DPSCs), and determine the underlying molecular mechanism involved. Methods: Alkaline phosphatase (ALP) activity, alizarin red staining, scratch migration assays and in vitro and in vivo osteo-/dentinogenic marker detection of bone-like tissue generation in nude mice were used to assess osteo-/dentinogenic differentiation. Coimmunoprecipitation and polypeptide microarray assays were employed to detect the molecular mechanisms involved. Results: The data revealed that knockdown of GREM1 promoted ALP activity, mineralisation in vitro and the expression of osteo-/dentinogenic differentiation markers and enhanced osteo-/ dentinogenesis of DPSCs in vivo. GREM1 bound to YWHAH in DPSCs, and the binding site was also identified. Knockdown of YWHAH suppressed the osteo-/dentinogenesis of DPSCs in vitro, and overexpression of YWHAH promoted the osteo-/dentinogenesis of DPSCs in vitro and in vivo. Conclusion: Taken together, the findings highlight the critical roles of GREM1-YWHAH in the osteo-/dentinogenesis of DPSCs.
- Subjects
DENTAL pulp; STEM cells; ALKALINE phosphatase; BINDING sites; ALIZARIN
- Publication
Chinese Journal of Dental Research, 2024, Vol 27, Issue 3, p203
- ISSN
1462-6446
- Publication type
Article
- DOI
10.3290/j.cjdr.b5698390