MiR-224-5p inhibits osteoblast differentiation and impairs bone formation by targeting Runx2 and Sp7.

IF 2 4区生物学 Q3 BIOTECHNOLOGY & APPLIED MICROBIOLOGY

Cytotechnology Pub Date : 2023-12-01 Epub Date: 2023-09-05 DOI:10.1007/s10616-023-00593-z

Siyang Ding, Yunfei Ma, Jiashu Yang, Yuting Tang, Yucui Jin, Lingyun Li, Changyan Ma

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引用次数: 0

Abstract

Osteoporosis is a complicated multifactorial disorder characterized by low bone mass and deteriorated bone microarchitecture with an elevated fracture risk. MicroRNAs play important roles in osteoblastic differentiation. In the present study, we found that miR-224-5p was markedly downregulated during the osteogenic differentiation of C2C12 cells. Overexpression of miR-224-5p in C2C12 cells inhibited osteoblast activity, as indicated by reduced ALP activity, matrix mineralization and the expression of osteogenic marker genes. Moreover, we demonstrated that Runx2 and Sp7 were direct targets of miR-224-5p. Furthermore, the specific inhibition of miR-224-5p by femoral bone marrow cavity injection with miR-224-5p antagomir prevented ovariectomy-induced bone loss. Finally, we found that the levels of miR-224-5p were markedly elevated in the sera of patients with osteoporosis. Collectively, this study revealed that miR-224-5p negatively regulates osteogenic differentiation by targeting Runx2 and Sp7. It also highlights the potential use of miR-224-5p as a therapeutic target and diagnostic biomarker for osteoporosis.

Supplementary information: The online version contains supplementary material available at 10.1007/s10616-023-00593-z.

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MiR-224-5p通过靶向Runx2和Sp7抑制成骨细胞分化并损害骨形成。

骨质疏松症是一种复杂的多因素疾病，其特征是骨量低，骨微结构恶化，骨折风险升高。微小RNA在成骨细胞分化中起着重要作用。在本研究中，我们发现miR-224-5p在C2C12细胞的成骨分化过程中显著下调。miR-224-5p在C2C12细胞中的过表达抑制了成骨细胞的活性，如ALP活性降低、基质矿化和成骨标记基因的表达所示。此外，我们证明Runx2和Sp7是miR-224-5p的直接靶标。此外，通过股骨髓腔注射miR-224-5p安他美对miR-224-5p的特异性抑制防止了卵巢切除术诱导的骨丢失。最后，我们发现骨质疏松症患者血清中miR-224-5p的水平显著升高。总之，这项研究揭示了miR-224-5p通过靶向Runx2和Sp7负调控成骨分化。它还强调了miR-224-5p作为骨质疏松症的治疗靶点和诊断生物标志物的潜在用途。补充信息：在线版本包含补充材料，网址为10.1007/s10616-023-00593-z。

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来源期刊

Cytotechnology 生物-生物工程与应用微生物

CiteScore

4.10

自引率

0.00%

发文量

审稿时长

6-12 weeks

期刊介绍： The scope of the Journal includes: 1. The derivation, genetic modification and characterization of cell lines, genetic and phenotypic regulation, control of cellular metabolism, cell physiology and biochemistry related to cell function, performance and expression of cell products. 2. Cell culture techniques, substrates, environmental requirements and optimization, cloning, hybridization and molecular biology, including genomic and proteomic tools. 3. Cell culture systems, processes, reactors, scale-up, and industrial production. Descriptions of the design or construction of equipment, media or quality control procedures, that are ancillary to cellular research. 4. The application of animal/human cells in research in the field of stem cell research including maintenance of stemness, differentiation, genetics, and senescence, cancer research, research in immunology, as well as applications in tissue engineering and gene therapy. 5. The use of cell cultures as a substrate for bioassays, biomedical applications and in particular as a replacement for animal models.