• International Journal of Stem Cells
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• v.15 no.3
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• pp.324-333
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• 2022

Background and Objectives: This study was to investigate the role of microRNA-29a-3p (miR-29a-3p) in human bone marrow mesenchymal stem cells (hBMSCs), and its relationship with steroid-associated osteonecrosis. Methods and Results: The online tool GEO2R was used to screen out the differentially expressed genes (DEGs) in GSE123568 dataset. Quantitative real time-polymerase chain reaction (qRT-PCR) was performed to detect the expression of miR-29a-3p, forkhead box O3 (FOXO3), alkaline phosphatase (ALP), bone gamma-carboxyglutamate protein (OCN) and RUNX family transcription factor 2 (Runx2) in the hBMSCs isolated from the patients with steroid-associated osteonecrosis. CCK-8 assay was executed to measure cell viability; western blot assay was utilized to detect FOXO3, ALP, Runx2, OCN and β-catenin expression. Cell apoptosis and cell cycle were detected by flow cytometry. Immunofluorescence assay was used to detect the sub-cellular localization of β-catenin. Bioinformatics analysis and luciferase reporter gene assay were performed to confirm whether miR-29a-3p can combine with FOXO3 3'UTR. MiR-29a-3p was markedly up-regulated in the hBMSCs of patients with steroid-associated osteonecrosis, while FOXO3 mRNA was significantly down-regulated. Transfection of miR-29a-3p mimics significantly inhibited the hBMSCs' proliferation, osteogenic differentiation markers' expressions, including ALP, Runx2, OCN, and repressed the ALP activity, as well as promoted cell apoptosis and cell-cycle arrest. FOXO3 was identified as a target gene of miR-29a-3p, and miR-29a-3p can inhibit the expression of FOXO3 and β-catenin, and inhibition of miR-29a-3p promoted translocation of β-catenin to the nucleus. Conclusions: MiR-29a-3p can modulate FOXO3 expression and Wnt/β-catenin signaling to inhibit viability and osteogenic differentiation of hBMSCs, thereby promoting the development of steroid-associated osteonecrosis.

• Journal of Korean Foot and Ankle Society
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• v.4 no.2
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• pp.83-86
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• 2000

A vascular necrosis of the talus has frequently been reported following trauma because talus has no muscle insertions, sixty percent of the surface of the talus is covered by hyaline cartilage, takes only a small area for entrance of a blood supply. Osteonecrosis is also associated with a variety of nontraumatic disorders. There are many indications for steroid usage, patient with rheumatoid arthritis, systemic lupus erythematosus, chronic obstructive pulmonary disease, and status- post renal or cardiac transplantation may be on long- term steroid usage, osteonecrosis may develop. A vascular necrosis of the talus secondary to chronic steroid usage is an unusual case. Delay in detection of osteonecrosis may lead to fragmentation and collapse of the talar body. When pain on range of motion is present and conservative treatment have been exhausted, surgical treatment is indicated, that is, fusion of the ankle joint. However it is important that conservative treatment may prevent its various sequelae with early diagnosis because steroid - treated patients have a more operative risk and increased risk for postoperative infection. We report a rare case of corticosteroid induced avascular necrosis of talus after cardiac transplantation.