Long non-coding RNA Homeobox D gene cluster antisense growth-associated long noncoding RNA/microRNA-182-5p/Homeobox protein A10 alleviates postmenopausal osteoporosis via accelerating osteoblast differentiation of bone marrow mesenchymal stem cells

Huang, YeJian; Tao, MingGao; Yan, ShiXian; He, XueMing

doi:10.1186/s13018-023-04203-8

Cited by 4 publications

(1 citation statement)

References 47 publications

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“…Up to now, several signaling pathways have been reported to participate in the regulation of osteogenic differentiation of BMSCs, and more and more methods have been developed to augment osteogenic differentiation. LncRNA HAGLR improved the osteogenic differentiation of BMSCs by affecting the miR-182-5p/Hoxa10 signaling pathway [ 36 ]. In mice models, BMSCs secreted exosomes, and then alleviated osteoporosis by regulating USP7/YAP1 and Wnt/β-catenin signaling pathways [ 37 ].…”

Section: Discussionmentioning

confidence: 99%

CRYAB suppresses ferroptosis and promotes osteogenic differentiation of human bone marrow stem cells via binding and stabilizing FTH1

Tian,

Li,

et al. 2024

Aging

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Background: Bone formation and homeostasis are greatly dependent on the osteogenic differentiation of human bone marrow stem cells (BMSCs). Therefore, revealing the mechanisms underlying osteogenic differentiation of BMSCs will provide new candidate therapeutic targets for osteoporosis. Methods: The osteogenic differentiation of BMSCs was measured by analyzing ALP activity and expression levels of osteogenic markers. Cellular Fe and ROS levels and cell viability were applied to evaluate the ferroptosis of BMSCs. qRT-PCR, Western blotting, and co-immunoprecipitation assays were harnessed to study the molecular mechanism. Results: The mRNA level of CRYAB was decreased in the plasma of osteoporosis patients. Overexpression of CRYAB increased the expression of osteogenic markers including OCN, OPN, RUNX2, and COLI, and also augmented the ALP activity in BMSCs, on the contrary, knockdown of CRYAB had opposite effects. IP-MS technology identified CRYAB-interacted proteins and further found that CRYAB interacted with ferritin heavy chain 1 (FTH1) and maintained the stability of FTH1 via the proteasome mechanism. Mechanically, we unraveled that CRYAB regulated FTH1 protein stability in a lactylation-dependent manner. Knockdown of FTH1 suppressed the osteogenic differentiation of BMSCs, and increased the cellular Fe and ROS levels, and eventually promoted ferroptosis. Rescue experiments revealed that CRYAB suppressed ferroptosis and promoted osteogenic differentiation of BMSCs via regulating FTH1. The mRNA level of FTH1 was decreased in the plasma of osteoporosis patients. Conclusions: Downregulation of CRYAB boosted FTH1 degradation and increased cellular Fe and ROS levels, and finally improved the ferroptosis and lessened the osteogenic differentiation of BMSCs.

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Section: Discussionmentioning

confidence: 99%

CRYAB suppresses ferroptosis and promotes osteogenic differentiation of human bone marrow stem cells via binding and stabilizing FTH1

Tian,

Li,

et al. 2024

Aging

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The role of LncRNAs and CircRNAs in osteoporosis: a focus on osteogenesis and osteoclastogenesis signaling pathways

Ismail,

Abd-Elmawla,

Shabayek

et al. 2024

Futur J Pharm Sci

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Background Osteoporosis is a crucial health concern interconnected with physical disabilities as well as financial burdens. It arises from an imbalance between osteoblasts and osteoclasts, provoking the reduction of bone mass and the disturbances in bone structure with high fracture risk. Considerable efforts were done to prevent and mitigate this public health issue. Nonetheless, further understanding of the etiopathology of osteoporosis and the underlying genetic and epigenetic pathways is required. Main body Emerging evidence indicates that noncoding RNAs, including long noncoding RNAs (lncRNAs) and circular RNAs (circRNAs), play crucial roles as epigenetic regulators in various pathological processes, including osteoporosis. LncRNAs are RNA transcripts with higher structural complexity that are developed owing to their secondary and tertiary structures, which allow them to create different binding sites for other biomolecules, such as DNA, RNA, and proteins. Another class of noncoding RNAs is circRNAs, which have a covalently closed loop structure without the 5′ cap and 3′ polyA tail and are formed by back-splicing of pre-mRNAs. Because of their closed structure, circRNAs are largely stable, resistant to RNA-degrading nucleases, and possess substantially longer circulatory half-lives than linear RNAs. Interestingly, both lncRNAs and circRNAs serve as competing endogenous RNAs by sponging multiple miRNA binding sites as well as interact with RNA-binding proteins (RBPs), thereby controlling the expression of their target genes. Several studies indicated that altered expression of these regulators could influence many biological processes in bone cells. Conclusion The current review provides current opinions on the role and the underlying mechanisms by which lncRNAs and circRNAs affect osteoblastic and osteoclastic activities. The deep understanding of these noncoding RNAs in osteoporosis offers distinctive avenues for innovative treatment strategies.

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The impact of light compressive stress on early bone remodeling and the expression profile of associated circRNAs

Yuan,

Xi,

Huang

et al. 2024

Preprint

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Objectives The effects of mechanical stress on bone remodeling have been constantly studied by researchers at different levels, however several aspects still exist which are considerably unclear. The aim of this study was to investigate the response of osteoblasts exposed to different levels of compressive stress, to identify and perform a comprehensive analysis of the circRNA expression pattern as well as investigate their potential regulatory roles. Methods The gene and protein expression levels of Runx2, Alp, OCN, Rankl, and Opg were examined in MC3T3-E1 cells after exposure to varying levels of compressive stress. Whole transcriptome sequencing and qRT-PCR were used to identify the various differentially expressed circRNAs. Furthermore, MiRanda, Gene Ontology, Kyoto Encyclopedia of Genes and Genomes and Reactome enrichment analysis were used to predict the potential functions of the differentially expressed circRNAs. Results The osteoblastic and osteoclastic differentiation effects on the bone tissues were enhanced at 2g/cm2. 99 differentially expressed circRNAs were identified by whole transcriptome sequencing. They were predicted to interact with 1701 miRNAs, some of which play a crucial part in regulating osteogenic differentiation via the Wnt or Notch pathway. Conclusions This study suggested that 2g/cm2 compressive stress was sufficient to induce osteogeneis and bone tissue resorption. This was the first study to identify differentially expressed circRNAs and to integrate their potential ceRNA function during early bone remodeling after exposure to light compressive stress. These findings suggest that certain specific circRNAs might possess the potential to function as ceRNAs in order to promote bone remodeling.

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Long non-coding RNA Homeobox D gene cluster antisense growth-associated long noncoding RNA/microRNA-182-5p/Homeobox protein A10 alleviates postmenopausal osteoporosis via accelerating osteoblast differentiation of bone marrow mesenchymal stem cells

Cited by 4 publications

References 47 publications

CRYAB suppresses ferroptosis and promotes osteogenic differentiation of human bone marrow stem cells via binding and stabilizing FTH1

CRYAB suppresses ferroptosis and promotes osteogenic differentiation of human bone marrow stem cells via binding and stabilizing FTH1

The role of LncRNAs and CircRNAs in osteoporosis: a focus on osteogenesis and osteoclastogenesis signaling pathways

The impact of light compressive stress on early bone remodeling and the expression profile of associated circRNAs

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