Dataset Information

Upregulating MicroRNA-410 or Downregulating Wnt-11 Increases Osteoblasts and Reduces Osteoclasts to Alleviate Osteonecrosis of the Femoral Head.

ABSTRACT:

Background

Little is known regarding the functional role of microRNA-410 (miR-410) in osteonecrosis of the femoral head (ONFH); hence, the aim of the present study was to investigate miR-410 targeting Wnt-11 to modulate the osteogenic and osteoclastic mechanism in the prevention of ONFH.

Methods

Fifteen ONFH samples and 15 normal samples were gathered. The pathological changes of the femoral head, osteoblasts, and osteoclasts in the clinical samples were observed. The rat model of ONFH was injected with agomir-miR-410, Wnt-11-siRNA, or oe-Wnt-11. MiR-410; Wnt-11; osteoblast-related factors alkaline phosphatase (ALP), bone gamma-carboxyglutamate protein (BGLAP), and Coll?1 expression; and osteoclast-related factors acid phosphatase 5 (ACP5), cathepsin K (CTSK), and MMP9, as well as Bcl-2 and Bax expression, were tested by RT-qPCR and western blot analysis. The osteogenic function index ALP and OCN together with osteoclast function index NTX-1 and CTX-1 in serum was tested by ELISA.

Results

MiR-410, ALP, BGLAP, and Coll?1 degraded as well as Wnt-11, ACP5, CTSK, and MMP9 enhanced in ONFH tissues of the clinical samples. Upregulated miR-410 and downregulated Wnt-11 enhanced bone mineral density (BMD) and BV/TV of rats, heightened the BMD level of the femoral shaft, femoral head, and spinal column, and also raised the serum calcium and phosphorus levels of rats, while restrained apoptosis of osteocytes, elevated OCN, ALP, BGLAP, and Coll?1 expression and declined ACP5, CTSK, NTX-1, CTX-1, and MMP9 expression in rats.

Conclusion

This study suggested that upregulating miR-410 or downregulating Wnt-11 increases osteoblasts and reduces osteoclasts to alleviate the occurrence of ONFH. Thus, miR-410 may serve as a potential target for the treatment of ONFH.

SUBMITTER: Yin Y

PROVIDER: S-EPMC6920280 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Upregulating MicroRNA-410 or Downregulating Wnt-11 Increases Osteoblasts and Reduces Osteoclasts to Alleviate Osteonecrosis of the Femoral Head.

Yin Yukun Y Ding Lixiang L Hou Yu Y Jiang Haoran H Zhang Ji J Dai Zhong Z Zhang Genai G

Nanoscale research letters 20191218 1

<h4>Background</h4>Little is known regarding the functional role of microRNA-410 (miR-410) in osteonecrosis of the femoral head (ONFH); hence, the aim of the present study was to investigate miR-410 targeting Wnt-11 to modulate the osteogenic and osteoclastic mechanism in the prevention of ONFH.<h4>Methods</h4>Fifteen ONFH samples and 15 normal samples were gathered. The pathological changes of the femoral head, osteoblasts, and osteoclasts in the clinical samples were observed. The rat model of ...[more]

PMID: 31853663

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Project description:The Buxue Tongluo pill (BTP) is a self-made pill with the functions of nourishing blood, promoting blood circulation, dredging collaterals, and relieving pain. It consists of Angelica sinensis (Oliv.) Diels, Pheretima aspergillum (E.Perrier), Panax notoginseng (Burk.) F. H. Chen, Astragalus membranaceus (Fisch.) Bge, and Glycyrrhiza uralensis Fisch. Various clinical practices have confirmed the therapeutic effect of BTP on osteonecrosis of the femoral head (ONFH), but little attention has been paid to the study of its bioactive ingredients and related mechanisms of action. In this study, UPLC/MS-MS combined with GEO data mining was used to construct a bioactive ingredient library of BTP and a differentially expressed gene (DEG) library for ONFH. Subsequently, Cytoscape (3.7.2) software was used to analyze the protein-protein interaction between BTP and DEGs of ONFH to screen the key targets, and functional annotation analysis and pathway enrichment analysis were carried out. Finally, 34 bioactive compounds were screened, which acted on 1,232 targets. A total of 178 DEGs were collected, and 17 key genes were obtained after two screenings. By bioinformatics annotation on these key genes, a total of 354 gene ontology (GO) functional annotation analyses and 42 Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were obtained. The present study found that GO and KEGG enrichment were mainly related to apoptosis, suggesting that BTP may exert an anti-ONFH effect by promoting osteoclast apoptosis. Experiments in vitro demonstrated that BTP could increase the mitochondrial membrane potential (MMP) and induce remarkable apoptosis in osteoclasts. Furthermore, we determined the apoptosis marker of cleaved(C)-caspase-3, bcl-2, and bax and found that BTP could upregulate the C-caspase-3 and bax expression in osteoclasts and decrease the expression of bcl-2, p-Akt, and p-PI3K in a dose-dependent manner, indicating that BTP could induce PI3K/Akt-mediated apoptosis in osteoclasts to treat ONFH. This study explored the pharmacodynamic basis and mechanism of BTP against ONFH from the perspective of systemic pharmacology, laying a foundation for further elucidating the therapeutic effects of BTP against ONFH.

Dataset Information

Upregulating MicroRNA-410 or Downregulating Wnt-11 Increases Osteoblasts and Reduces Osteoclasts to Alleviate Osteonecrosis of the Femoral Head.

Background

Methods

Results

Conclusion

Publications

Upregulating MicroRNA-410 or Downregulating Wnt-11 Increases Osteoblasts and Reduces Osteoclasts to Alleviate Osteonecrosis of the Femoral Head.

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