GREM1 通过与 YWHAH 结合负调控牙髓干细胞的成骨/成牙本质分化。

GREM1 Negatively Regulates Osteo-/Dentinogenic Differentiation of Dental Pulp Stem Cells via Association with YWHAH.

出版信息

Chin J Dent Res. 2024 Sep 2;27(3):203-213. doi: 10.3290/j.cjdr.b5698390.

DOI:10.3290/j.cjdr.b5698390

PMID:39221981

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.

摘要

目的

研究 Gremlin1（GREM1）和酪氨酸 3-单加氧酶/色氨酸 5-单加氧酶激活蛋白 eta（YWHAH）在牙髓干细胞（DPSCs）中的生物学调节功能，并确定相关的分子机制。

方法

碱性磷酸酶（ALP）活性、茜素红染色、划痕迁移实验以及在裸鼠体内检测骨样组织生成的体外和体内成骨/成牙本质标志物检测，用于评估成骨/成牙本质分化。采用免疫共沉淀和多肽微阵列分析检测相关的分子机制。

结果

数据显示，GREM1 敲低促进了 DPSCs 的 ALP 活性、体外矿化以及成骨/成牙本质分化标志物的表达，并增强了 DPSCs 在体内的成骨/成牙本质分化。GREM1 与 DPSCs 中的 YWHAH 结合，并且确定了结合位点。YWHAH 敲低抑制了 DPSCs 的体外成骨/成牙本质分化，而过表达 YWHAH 则促进了 DPSCs 的体外和体内成骨/成牙本质分化。