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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Kaiso 通过 Itga10/PI3K/AKT 信号通路调节成骨细胞分化和矿化
DOI：
10.3892/ijmm.2021.4874
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发表时间：
2021-02
期刊：
影响因子：
--
通讯作者：
Weidong Xu
中科院分区：
文献类型：
--
作者：
Wenwen Tong;Jia Li;Xinzhe Feng;Chen Wang;Yihong Xu;Chongru He;Weidong Xu
骨形成和骨吸收之间的动态平衡维持着骨的动态平衡。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在多种细胞中被认为是细胞增殖和分化的调节因子。然而，目前对其在骨骼内稳态中的作用的研究还很缺乏。在本研究中，通过细胞和动物实验来研究Kaiso在骨稳态中的作用。本研究证实Kaiso基因在MC3T3-E1细胞成骨分化过程中表达下调。MC3T3-E1细胞的功能获得和功能丧失研究表明，Kaiso在体外成骨细胞分化中起着关键作用。这一发现在体内得到了进一步证实。序列分析结果表明，Kaiso通过调节PI3K/AKT信号通路影响成骨细胞的分化和矿化。此外，整合素亚单位α10(ITGA10)通过染色质免疫沉淀和荧光素酶报告基因分析被确定为Kaiso的直接靶标。总之，这些发现表明Kaiso通过ITGA10/PI3K/AKT途径调节成骨细胞的分化，这代表了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.
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影响因子：
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作者：
Onizuka, Satoru;Iwata, Takanori;Park, Sung-Joon;Nakai, Kenta;Yamato, Masayuki;Okano, Teruo;Izumi, Yuichi
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DOI：
10.1101/2023.07.06.23292311
发表时间：
2023-07
期刊：
medRxiv : the preprint server for health sciences
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作者：
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影响因子：
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