Chondrocyte mTORC1 activation stimulates miR-483-5p via HDAC4 in osteoarthritis progression

Journal of Cellular Physiology
Hua WangXiaochun Bai

Abstract

The hyperactivation of the mechanistic target of rapamycin complex 1 (mTORC1) in chondrocytes has been shown to accelerate the severity of destabilization of the medial meniscus-induced and age-related osteoarthritis (OA) phenotypes with aberrant chondrocyte hypertrophy and angiogenesis. Meanwhile, we previously reported that miR-483-5p is essential for the initiation and development of OA by stimulating chondrocyte hypertrophy and angiogenesis. The connection between mTORC1 and miR-483-5p activation in OA progression, however, remains unclear. In this study, we elucidated their relationship and identified the underlying mechanisms. The expression of miR-483-5p in the articular cartilage of cartilage-specific TSC1 knockout mice was assessed compared with control mice using the Agilent Mouse miRNA (8*60K) V19.0 array and real-time polymerase chain reaction (RT-PCR). The functional effects of the stimulation of miR-483-5p via histone deacetylase 4 (HDAC4) by mTORC1 in OA development, subsequently modulating its downstream targets matrilin 3 and tissue inhibitor of metalloproteinase 2, were examined by immunostaining, western blotting, and real-time PCR. This study revealed that miR-483-5p was responsible for mTORC1 activation-sti...Continue Reading

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Citations

Oct 27, 2020·Frontiers in Cell and Developmental Biology·He ZhangLunhao Bai
Feb 22, 2021·Molecular and Cellular Biochemistry·Tao PengYankai Jiang
Jun 15, 2021·Hormone and Metabolic Research = Hormon- Und Stoffwechselforschung = Hormones Et Métabolisme·Lu LiuYexu Song
Dec 11, 2021·Frontiers in Pharmacology·Jinxia DengBo Wei

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