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Upregulation of microRNA-9-5p inhibits apoptosis of chondrocytes through downregulating Tnc in mice with osteoarthritis following tibial plateau fracture
Authors:Hongwei Chen  Jun Yang  Zhihong Tan
Affiliation:1. Department of Orthopedics, Yiwu Central Hospital, Affiliated Hospital of Wenzhou Medical University, Yiwu, People's Republic of China

Hongwei Chen and Jun Yang contributed equally to this work.;2. Department of Orthopedics, The Affiliated Hospital of Xinyang Vocational and Technical College, Xinyang, People's Republic of China

Hongwei Chen and Jun Yang contributed equally to this work.;3. Department of Orthopaedics, Huizhou Hospital of Traditional Chinese Medicine, Huizhou, People's Republic of China

Abstract:Osteoarthritis (OA) is a common degenerative joint disease which is typically progressed with age, affecting smaller joints of hands, lower limbs, and the vertebral column. It has been reported that microRNAs could regulate the biological processes of OA. Therefore, the purpose of this study was to elucidate miR-9-5p's role in regulating cartilage remodeling of OA mice following tibial plateau fracture (TPF) through regulation of tenascin C (Tnc). Initially, we determined the expression of miR-9-5p and Tnc in mice with OA and then testified their relationship. The results displayed a high expression of Tnc, but a poor expression of miR-9-5p with high methylation in OA. Tnc was confirmed to be a target gene of miR-9-5p. Moreover, based on gain- and loss-function experiments, an increase of miR-9-5p and loss of Tnc had the potential to inhibit cell apoptosis, while facilitating cell proliferation, migration, invasion, and cartilage remodeling of mice with OA following TPF. This was further demonstrated by a higher expression of type II collagen, lower type X collagen, and protogenin expression. Subsequently, downregulation of miR-9-5p aggravated the pathological changes of mice, illustrated by an increase in the Mankin score. In conclusion, the present study proved that overexpression of miR-9-5p suppressed chondrocytes apoptosis and promoted cartilage remodeling through downregulating of Tnc in mice with OA.
Keywords:cartilage remodeling  microRNA-9-5p  osteoarthritis  tibial plateau fracture  Tnc
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