Dataset Information

Kaiso regulates osteoblast differentiation and mineralization via the Itga10/PI3K/AKT signaling pathway.

ABSTRACT: Bone homeostasis is maintained by a dynamic balance between bone formation and bone resorption. The cellular activities of osteoblasts and osteoclasts are the primary factors that maintain this dynamic balance. The transcription factor Kaiso has been identified as a regulator of cell proliferation and differentiation in various cells. However, research into its role in bone homeostasis is currently lacking. In the present study, cell and animal experiments were conducted to investigate the role of Kaiso in bone homeostasis. The present study identified that Kaiso was downregulated during osteoblast differentiation in MC3T3?E1 cells. Gain? and loss?of?function studies in MC3T3?E1 cells demonstrated that Kaiso served a critical role in osteoblast differentiation in vitro. The findings were further confirmed in vivo. The results of the sequence analysis indicated that Kaiso influenced osteoblast differentiation and mineralization by regulating the PI3K/AKT signaling pathway. Moreover, integrin subunit ?10 (Itga10) was identified as a direct target of Kaiso via chromatin immunoprecipitation and luciferase reporter assays. Collectively, these findings suggested that Kaiso regulated the differentiation of osteoblasts via the Itga10/PI3K/AKT pathway, which represents a therapeutic target for bone formation or bone resorption?related diseases.

SUBMITTER: Tong W

PROVIDER: S-EPMC7891822 | biostudies-literature | 2021 Apr

REPOSITORIES: biostudies-literature

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Kaiso regulates osteoblast differentiation and mineralization via the Itga10/PI3K/AKT signaling pathway.

Tong Wenwen W Li Jia J Feng Xinzhe X Wang Chen C Xu Yihong Y He Chongru C Xu Weidong W

International journal of molecular medicine 20210212 4

Bone homeostasis is maintained by a dynamic balance between bone formation and bone resorption. The cellular activities of osteoblasts and osteoclasts are the primary factors that maintain this dynamic balance. The transcription factor Kaiso has been identified as a regulator of cell proliferation and differentiation in various cells. However, research into its role in bone homeostasis is currently lacking. In the present study, cell and animal experiments were conducted to investigate the role ...[more]

PMID: 33576467

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Project description:Cutaneous squamous carcinoma is the second most common epithelial malignancy, associated with significant morbidity, mortality, and economic burden. However, the mechanisms underlying cSCC remain poorly understood. In this study, we identified TGM3 as a novel cSCC tumor suppressor that acts via the PI3K-AKT axis. RT-qPCR, IHC and western blotting were employed to assess TGM3 levels. TGM3-overexpression/knockdown cSCC cell lines were utilized to detect TGM3's impact on epithelial differentiation as well as tumor cell proliferation, migration, and invasion in vitro. Additionally, subcutaneous xenograft tumor models were employed to examine the effect of TGM3 knockdown on tumor growth in vivo. Finally, molecular and biochemical approaches were employed to gain insight into the tumor-suppressing mechanisms of TGM3. TGM3 expression was increased in well-differentiated cSCC tumors, whereas it was decreased in poor-differentiated cSCC tumors. Loss of TGM3 is associated with poor differentiation and a high recurrence rate in patients with cSCC. TGM3 exhibited tumor-suppressing activity by regulating cell proliferation, migration, and invasion both in vitro and in vivo. As a novel cSCC tumor differentiation marker, TGM3 expression was positively correlated with cell differentiation. In addition, our results demonstrated an interaction between TGM3 and KRT14 that aids in the degradation of KRT14. TGM3 deficiency disrupts keratinocytes differentiation, and ultimately leads to tumorigenesis. Furthermore, RNA-sequence analysis revealed that loss of TGM3 enhanced EMT via the PI3K-AKT signaling pathway. Deguelin, a PI3K-AKT inhibitor, blocked cSCC tumor growth induced by TGM3 knockdown in vivo. Taken together, TGM3 inhibits cSCC tumor growth via PI3K-AKT signaling, which could also serve as a tumor differentiation marker and a potential therapeutic target for cSCC. Proposed model depicted the mechanism by which TGM3 suppress cSCC development. TGM3 reduces the phosphorylation level of AKT and degrades KRT14. In the epithelial cell layer, TGM3 exhibits a characteristic pattern of increasing expression from bottom to top, while KRT14 and pAKT are the opposite. Loss of TGM3 leads to reduced degradation of KRT14 and activation of pAKT, disrupting keratinocyte differentiation, and eventually resulting in the occurrence of low-differentiated cSCC.

Dataset Information

Kaiso regulates osteoblast differentiation and mineralization via the Itga10/PI3K/AKT signaling pathway.

Publications

Kaiso regulates osteoblast differentiation and mineralization via the Itga10/PI3K/AKT signaling pathway.

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