Krishnan R Hari, Sadu Lakshana, Akshaya R L, Gomathi K, Saranya I, Das Udipt Ranjan, Satishkumar Sneha, Selvamurugan N
Department of Biotechnology, College of Engineering and Technology, SRM Institute of Science and Technology, Kattankulathur 603 203, Tamil Nadu, India.
Department of Biotechnology, College of Engineering and Technology, SRM Institute of Science and Technology, Kattankulathur 603 203, Tamil Nadu, India.
Int J Biol Macromol. 2023 Jan 15;225:1152-1163. doi: 10.1016/j.ijbiomac.2022.11.176. Epub 2022 Nov 22.
Parathyroid hormone (PTH) regulates the expression of bone remodeling genes by enhancing the activity of Runx2 in osteoblasts. p300, a histone acetyltransferase, acetylated Runx2 to activate the expression of its target genes. PTH stimulated the expression of p300 in rat osteoblastic cells. Increasing studies suggested the potential of non-coding RNAs (ncRNAs), such as microRNAs (miRNAs) and circular RNAs (circRNAs), in regulating gene expression under both physiological and pathological conditions. In this study, we hypothesized that PTH regulates Runx2 activity via ncRNAs-mediated p300 expression in rat osteoblastic cells. Bioinformatics and experimental approaches identified PTH-upregulation of miR-130b-5p and circ_CUX1 that putatively target p300 and miR-130b-5p, respectively. An antisense-mediated knockdown of circ_CUX1 was performed to determine the sponging activity of circ_CUX1. Knockdown of circ_CUX1 promoted miR-130b-5p activity and reduced p300 expression, resulting in decreased Runx2 acetylation in rat osteoblastic cells. Further, bioinformatics analysis identified the possible signaling pathways that regulate Runx2 activity and osteoblast differentiation via circ_CUX1/miR-130b-5p/p300 axis. The predicted circ_CUX1/miR-130b-5p/p300 axis might pave the way for better diagnostic and therapeutic approaches for bone-related diseases.
甲状旁腺激素（PTH）通过增强成骨细胞中Runx2的活性来调节骨重塑基因的表达。p300是一种组蛋白乙酰转移酶，可使Runx2乙酰化以激活其靶基因的表达。PTH刺激大鼠成骨细胞中p300的表达。越来越多的研究表明，非编码RNA（ncRNA），如微小RNA（miRNA）和环状RNA（circRNA），在生理和病理条件下调节基因表达方面具有潜力。在本研究中，我们假设PTH通过ncRNA介导的p300表达在大鼠成骨细胞中调节Runx2活性。生物信息学和实验方法确定了miR-130b-5p和circ_CUX1的PTH上调，它们分别可能靶向p300和miR-130b-5p。进行了反义介导的circ_CUX1敲低以确定circ_CUX1的海绵活性。circ_CUX1的敲低促进了miR-130b-5p的活性并降低了p300的表达，导致大鼠成骨细胞中Runx2乙酰化减少。此外，生物信息学分析确定了通过circ_CUX1/miR-130b-5p/p300轴调节Runx2活性和成骨细胞分化的可能信号通路。预测的circ_CUX1/miR-130b-5p/p300轴可能为骨相关疾病的更好诊断和治疗方法铺平道路。
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