title: Involvement of MicroRNA-210 Demethylation in Steroid-associated Osteonecrosis of the Femoral Head.
abstract: Angiogenesis is an important event in steroid-associated osteonecrosis of the femoral head (SONFH). Here we performed miRNA microarray with SONFH tissues (ONs) and the adjacent normal tissues (NLs) to select the angiogenic miRNA. The results showed that miR-210 was differentially expressed in SONFH versus normal tissues. Unexpectedly, its specific transcription factor, hypoxia-inducible factor-1α, was shown of no significant changes in ONs compared with NLs. Further Bisulfite sequencing revealed that miR-210 is embedded in a CpG island and miR-210 gene has 2 CpG sites with lower methylation percentage in ONs compared with NLs. Additionally, ONs with lower miR-210 gene methylation exhibited higher miR-210 expression. Next, we found that the endothelial cells treated with demethylating agents could significantly increase the expression of miR-210, along with promoted cell viability and differentiation. Some angiogenic genes (VEGF, bFGF, TNF-α and PCNA) were up-regulated as well. In addition, the supernatant of the cells after demethylation treatment displayed an enhanced ability of recruiting new microvessels in vivo. Taken together, our study not only provides novel insights into the regulation of angiogenesis in this disease, but also reveals a therapeutic opportunity for treatment of SONFH patients with demethylating agents.
authors.affiliation: Department of Orthopedics, Zhongshan Hospital, Fudan University, Shanghai, China.|Department of Cancer Biology, Mayo Clinic, Florida, USA.
authors.forename: Heng-feng
authors.initials: HF
authors.lastname: Yuan
authors.affiliation: Department of Cancer Biology, Mayo Clinic, Florida, USA.|Mayo Graduate School, Mayo Clinic, Rochester, USA.
authors.forename: Von Roemeling
authors.initials: VR
authors.lastname: Christina
authors.affiliation: Department of Orthopedics, Zhongshan Hospital, Fudan University, Shanghai, China.
authors.forename: Chang-an
authors.initials: CA
authors.lastname: Guo
authors.affiliation: Department of Immunology, School of Basic Medical Science, Fudan University, Shanghai, China.
authors.forename: Yi-wei
authors.initials: YW
authors.lastname: Chu
authors.affiliation: Department of Immunology, School of Basic Medical Science, Fudan University, Shanghai, China.
authors.forename: Rong-hua
authors.initials: RH
authors.lastname: Liu
authors.affiliation: Department of Orthopedics, Zhongshan Hospital, Fudan University, Shanghai, China.
authors.forename: Zuo-qin
authors.initials: ZQ
authors.lastname: Yan
mesh_terms: D000328:Adult; D002454:Cell Differentiation / Q000235:genetics; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000235:genetics; D018899:CpG Islands / Q000235:genetics; D019175:DNA Methylation / Q000235:genetics*; D005260:Female; D005270:Femur Head / Q000378:metabolism / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000096:biosynthesis; D035683:MicroRNAs / Q000096:biosynthesis / Q000235:genetics*; D009389:Neovascularization, Pathologic / Q000235:genetics* / Q000473:pathology; D010020:Osteonecrosis / Q000235:genetics* / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
chemical_list: C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; C543800:MIRN210 microRNA, human; D035683:MicroRNAs; D014409:Tumor Necrosis Factor-alpha