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Hsa_circularRNA_0079201 suppresses chondrocyte proliferation and endochondral ossification by regulating the microRNA?140?3p/SMAD2 signaling pathway in idiopathic short stature.

ABSTRACT: Circular (circ)RNAs are an important group of non?coding RNAs involved in different pathological and physiological functions, such as longitudinal bone growth. However, the effects of an increase or decrease in circRNA expression on idiopathic short stature (ISS) remain largely unknown. The present study compared the circRNA expression patterns of patients with ISS and healthy individuals to identify differentially expressed circRNAs involved in the regulation of ISS pathogenesis and their target microRNAs (miR). Microarray analysis revealed that 145 circRNAs were differentially expressed in patients with ISS, including 83 up? and 62 downregulated circRNAs. Reverse transcription?quantitative PCR confirmed that hsa_circRNA_0079201 was increased in patients with ISS compared with that in the normal individuals, whilst hsa_circRNA_0079201 overexpression in human chondrocytes was shown to significantly suppress their proliferation, hypertrophy and endochondral ossification abilities. Luciferase reporter assays identified that circRNA_0079201 acted as an miR?140?3p sponge. In situ hybridization confirmed the co?localization of circRNA_0079201 and miR?140?3p in the human chondrocyte and neonatal femur growth plate of C57 mice, while rescue experiments demonstrated that miR?140?3p overexpression reversed the inhibition of human chondrocyte proliferation, hypertrophy and endochondral ossification, caused by circRNA_0079201 overexpression. Bioinformatics analysis and luciferase reporter assays revealed that SMAD2 was a potential target gene of miR?140?3p. Furthermore, overexpressing circRNA_0079201 in human chondrocytes suppressed miR?140?3p and increased SMAD2 protein expression level. Taken together, chondrocyte proliferation, hypertrophy and endochondral ossification in ISS was suppressed by a novel regulatory axis consisting of the hsa_circRNA_0079201/miR?140?3p/SMAD2 pathway. The present study provided evidence that hsa_circRNA_0079201 may be a potential target for ISS therapy.

SUBMITTER: Liu X

PROVIDER: S-EPMC7595675 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature

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Hsa_circularRNA_0079201 suppresses chondrocyte proliferation and endochondral ossification by regulating the microRNA‑140‑3p/SMAD2 signaling pathway in idiopathic short stature.

Liu Xijuan X Yan Chen C Deng Xueqiang X Jia Jingyu J

International journal of molecular medicine 20200925 6

Circular (circ)RNAs are an important group of non‑coding RNAs involved in different pathological and physiological functions, such as longitudinal bone growth. However, the effects of an increase or decrease in circRNA expression on idiopathic short stature (ISS) remain largely unknown. The present study compared the circRNA expression patterns of patients with ISS and healthy individuals to identify differentially expressed circRNAs involved in the regulation of ISS pathogenesis and their targe ...[more]

PMID: 33125098

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Project description:A variety of cell cultures models and in vivo approaches have been used to study gene expression during chondrocyte differentiation. The extent to which the in vitro models reflect bona fide gene regulation in the growth plate has not been quantified. In addition, studies that evaluate global gene expression changes among different growth plate zones are limited. To address these issues, we completed a microarray screen of three growth plate zones derived from manually segmented embryonic mouse tibiae. Classification of genes differentially expressed between each respective growth plate zone, functional categorization as well as characterization of gene expression patterns, cytogenetic loci, signaling pathways and functional motifs confirmed documented data and pointed to novel aspects of chondrocyte differentiation. Parallel comparisons of the microdissected tibiae data set to our previously completed micromass culture screen further corroborated the suitability of micromass cultures for modeling gene expression in chondrocyte development. The micromass culture system demonstrated striking similarities to the in vivo microdissected tibiae screen; however, the micromass system was unable to accurately distinguish gene expression differences in the hypertrophic and mineralized zones of the growth plate. These studies will allow us to better understand zone-specific gene expression patterns in the growth plate. Ultimately, this work will help define both the genomic context in which genes are expressed in the long bones and the extent to which the micromass culture system is able to recapitulate chondrocyte development in endochondral ossification. Experiment Overall Design: Tibiae from 15.5 day old mouse embryos were isolated and partitioned into three distinct zones. Total RNA was isolated from each segment and the individual segments pooled within a litter. Experiment Overall Design: Samples were hybridized to Affymetrix MOE 430 2.0 mouse chips for analysis. Four independent trials were executed for each zone. Experiment Overall Design: Number of time points: 1 Experiment Overall Design: Number of treatments: 0 Experiment Overall Design: Number of Samples: 4 replicates per zone Experiment Overall Design: Affymetrix chip: MOE 430 2.0 Experiment Overall Design: Tissue or origin: Tibiae Experiment Overall Design: Species E15.5 mice Experiment Overall Design: Samples: Total RNA

Dataset Information

Hsa_circularRNA_0079201 suppresses chondrocyte proliferation and endochondral ossification by regulating the microRNA?140?3p/SMAD2 signaling pathway in idiopathic short stature.

Publications

Hsa_circularRNA_0079201 suppresses chondrocyte proliferation and endochondral ossification by regulating the microRNA‑140‑3p/SMAD2 signaling pathway in idiopathic short stature.

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