Dataset Information

Osteocytic HIF-1α Pathway Manipulates Bone Micro-structure and Remodeling via Regulating Osteocyte Terminal Differentiation.

ABSTRACT: The activation of hypoxia-inducible factor 1α (HIF-1α) signaling has promising implications for the treatment of bone diseases such as osteoporosis and skeletal fractures. However, the effects of manipulating HIF-1α pathway on bone micro-structure and remodeling should be fully studied before the clinical application of therapeutics that interfere with the HIF-1α pathway. In this study, we found that osteocyte-specific HIF-1α pathway had critical role in manipulating bone mass accrual, bone material properties and micro-structures, including bone mineralization, bone collagen fiber formation, osteocyte/canalicular network, and bone remodeling. In addition, our results suggest that osteocyte-specific HIF-1α pathway regulates bone micro-structure and remodeling via impairing osteocyte differentiation and maturation.

SUBMITTER: Chen K

PROVIDER: S-EPMC8804240 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

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Osteocytic HIF-1α Pathway Manipulates Bone Micro-structure and Remodeling via Regulating Osteocyte Terminal Differentiation.

Chen Kaizhe K Zhao Jian J Qiu Minglong M Zhang Lianfang L Yang Kai K Chang Leilei L Jia Peng P Qi Jin J Deng Lianfu L Li Changwei C

Frontiers in cell and developmental biology 20220118

The activation of hypoxia-inducible factor 1α (HIF-1α) signaling has promising implications for the treatment of bone diseases such as osteoporosis and skeletal fractures. However, the effects of manipulating HIF-1α pathway on bone micro-structure and remodeling should be fully studied before the clinical application of therapeutics that interfere with the HIF-1α pathway. In this study, we found that osteocyte-specific HIF-1α pathway had critical role in manipulating bone mass accrual, bone mate ...[more]

PMID: 35118061

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Project description:CircRNAs play an important role in various physiological and pathological biological processes. Despite their widespread involvement, the function of circRNAs in intermittent hypoxia (IH) remain incompletely understood. This study aims to clarify the molecular mechanism of it in IH. Differentially expressed circRNAs were identified by transcriptome sequencing analysis in intermittent hypoxia (IH) model. GO and KEGG enrichment analys were performed on the identified differentially expressed circRNAs. The circular characteristics of hsa_circ_0081065 in human umbilical vein endothelial cells (HUVECs) were detected by RT-qPCR. The sublocalization of hsa_circ_0081065 was examined by FISH. The effect of hsa_circ_0081065 on endothelial to mesenchymal transition (EndMT) was estimated by detecting the expression of EndMT related markers. Various techniques, including RNA-pull down, RIP, EMSA, dual-luciferase reporter assay and immunofluorescence staining were used to investigate the relationship among hsa_circ_0081065, miR-665 and HIF-1α. A total of 13,304 circRNAs were identified in HUVECs treatment with IH, among which 73 were differentially expressed, including 24 upregulated circRNAs and 49 downregulated circRNAs. Notably, hsa_circ_0081065 demonstrated a significantly upregulation. Hsa_circ_0081065 exhibited the circular characteristics of circRNA and was predominantly localized in the cytoplasm. Knockdown of hsa_circ_0081065 inhibited EndMT. Mechanically, we demonstrated that hsa_circ_0081065 acts as a sponge for miR-665 to up-regulate HIF-1α and exacerbate HIF-1α nuclear translocation in HUVECs. We have demonstrated that hsa_circ_0081065 is significantly upregulated in HUVECs treated with IH. Our findings indicate that hsa_circ_0081065 exacerbates IH-induced EndMT through the regulation of the miR-665/HIF-1α signal axis and facilitating HIF-1α nuclear translocation. These results provide a theoretical basis for considering of EndMT as a potential therapeutic target for OSAHS intervention.

Dataset Information

Osteocytic HIF-1α Pathway Manipulates Bone Micro-structure and Remodeling via Regulating Osteocyte Terminal Differentiation.

Publications

Osteocytic HIF-1α Pathway Manipulates Bone Micro-structure and Remodeling via Regulating Osteocyte Terminal Differentiation.

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