Overexpressed miR-196a accelerates osteogenic differentiation in osteoporotic mice via GNAS-dependent Hedgehog signaling pathway
Autor: | Yu‐Zhu Zhang, Xiu‐Juan Jia, Hui‐Ling Fu, Li‐Na Zhong, Hong Li, Cheng‐Xiu Lv |
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Rok vydání: | 2018 |
Předmět: |
musculoskeletal diseases
0301 basic medicine Small interfering RNA Stromal cell Enzyme-Linked Immunosorbent Assay Biochemistry Metabolic bone disease 03 medical and health sciences Mice 0302 clinical medicine Osteogenesis medicine GNAS complex locus Animals Hedgehog Proteins Molecular Biology Bone mineral biology Chemistry Reverse Transcriptase Polymerase Chain Reaction Cell Differentiation Cell Biology medicine.disease Hedgehog signaling pathway RUNX2 Mice Inbred C57BL MicroRNAs 030104 developmental biology medicine.anatomical_structure 030220 oncology & carcinogenesis Cancer research biology.protein Osteoporosis Female Bone marrow Signal Transduction |
Zdroj: | Journal of cellular biochemistry. 120(12) |
ISSN: | 1097-4644 |
Popis: | Osteoporosis (OP), a common metabolic bone disease, is accompanied by reduced bone mass, bone mineral density (BMD), as well as microstructure destruction of bone. Previously, microRNA-196a-2 (miR-196a-2) and miR-196a-3p were reported for its involvement in BMD. Herein, this study set out to identify the functional relevance of miR-196a in osteogenic differentiation in osteoporotic mice and explore the associated mechanism by establishing an OP mouse model. Guanine nucleotide binding protein, alpha stimulating (GNAS) was verified as a target gene of miR-196a, which was decreased in OP mice. Furthermore, the bone marrow stromal cells (BMSCs) were then extracted from OP mice and treated with miR-196 mimic/inhibitor or small interfering RNA against GNAS to investigate miR-196a interaction with GNAS and the Hedgehog signaling pathway. BMSCs in OP mice transfected with miR-196a mimic or si-GNAS displayed the elevated expression of Smo, ALP, Runx2, and OPN, as well as bone gla protein and tartrate-resistant acid phosphatase, elevated ALP vitality and bone formation ability as well as reduced expression of GNAS and PTCH. Taken conjointly, overexpression of miR-196a repressed GNAS expression by activating the Hedgehog signaling pathway, thus promoting osteogenic differentiation in mice with OP. |
Databáze: | OpenAIRE |
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