Kaiso regulates osteoblast differentiation and mineralization via the Itga10/PI3K/AKT signaling pathway.
Kaiso regulates osteoblast differentiation and mineralization via the Itga10/PI3K/AKT signaling pathway.
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DOI：
10.3892/ijmm.2021.4874
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发表时间：
2021-04
影响因子：
5.4
通讯作者：
Xu W
中科院分区：
文献类型：
--
作者：
Tong W;Li J;Feng X;Wang C;Xu Y;He C;Xu W
骨稳态通过骨形成和骨吸收之间的动态平衡来维持。成骨细胞和破骨细胞的细胞活动是维持这种动态平衡的主要因素。转录因子Kaiso已被鉴定为各种细胞中细胞增殖和分化的调节因子。然而，目前缺乏对其在骨稳态中作用的研究。在本研究中，细胞和动物实验进行了调查Kaiso在骨稳态的作用。本研究确定Kaiso在MC 3 T3-E1细胞成骨分化过程中下调。MC 3 T3-E1细胞的功能获得和丧失研究表明，Kaiso在体外成骨细胞分化中起关键作用。这些发现在体内得到了进一步证实。序列分析结果表明，Kaiso通过调控PI 3 K/AKT信号通路影响成骨细胞的分化和矿化。此外，整合素亚基α10（Itga 10）通过染色质免疫沉淀和荧光素酶报告基因测定被鉴定为Kaiso的直接靶点。总的来说，这些发现表明Kaiso通过Itga 10/PI 3 K/AKT途径调节成骨细胞的分化，这是骨形成或骨吸收相关疾病的治疗靶点。
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 α10 (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.