Long noncoding RNA TM1P3 is involved in osteoarthritis by mediating chondrocyte extracellular matrix degradation

Abstract

Background and Objectives: Osteoarthritis (OA) is a widespread degenerative joint disease characterized by articular cartilage degradation and is the leading cause of physical disability. Noncoding RNAs, especially long noncoding RNAs (lncRNAs) and microRNAs, are involved in the degradation of the chondrocyte extracellular matrix (ECM) in patients with OA. The present study was aimed to investigate the effects of lncRNA and miR-22 on the degradation of the chondrocyte ECM and underlying mechanisms. Methods: To simulate conditions found in OA, primary cultured chondrocytes were treated with IL-1, TGF-β, or sb525334. Real-time PCR and Western blot analysis were performed to detect expressions of miR-22, lncRNA-TM1P3, ALK1, MMP13, pSMAD1/5, SMAD1, and pSMAD5. Small interfering RNAs and a miR-22 mimic or inhibitor were utilized to determine lncRNA-TM1P3 knockdown and miR-22 overexpression or inhibition.Results: The lncRNA-TM1P3 significantly upregulated in patients with OA, accompanied by the downregulation of miR-22 and upregulation of pSMAD1/5 and MMP13, which ultimately resulted in the degradation of the chondrocyte ECM in patients with OA. Bioinformatics analysis predicted miR-22 as a target of both lncRNA-TM1P3 and MMP13. The lncRNA-TM1P3 knockdown significantly increased the expression of ALK1, a corresponding increase in ECM degradation was observed by affecting the phosphorylation of SMAD1/5 and the expression of MMP13, which did not affect the expression of ALK1.Conclusions: These findings demonstrated that the lncRNA-TM1P3/miR-22/ TGF-β signaling/MMP13 axis is involved in the degradation of chondrocyte ECM in patients with OA, which could provide novel therapies for OA treatment.

MicroRNAs in Tumor Endothelial Cells: Regulation, Function and Therapeutic Applications

“…This mechanism possibly contributes to the observed downregulation of miR-22 in TECs of human NSCLC samples [ 59 ]. These findings are in line with previous studies showing that IL-1 downregulates the expression of miR-22 in primary cultured chondrocytes [ 114 ]. Moreover, NF-κB directly binds to the miR-22 promoter and inhibits the transcription of this miRNA in 182R-6 breast cancer cells [ 115 ].…”

Effects of microRNA-27a Targeting Smad1 on Intervertebral Disc Degeneration and Biological Characteristics of Nucleus Pulposus Cells

“…Barruet et al [26] showed that activation of the BMP4/Smad1 pathway could increase the expression of matrix brosis protein. Li et al [27] showed that long-chain noncoding RNA TM1P3 was upregulated in osteoarthritis. Notably, downregulation of its expression could decrease the phosphorylation levels of Smad1 and promote ECM degradation, suggesting that Smad1 was negatively related to ECM degradation.…”

The emerging role of lncRNAs in osteoarthritis development and potential therapy

“…LncRNA FOXD2-AS1 facilitated proliferation of chondrocytes via suppression of miR-27a-3p in osteoarthritis ( Wang et al, 2019b ). LncRNA TM1P3 mediated ECM degradation of chondrocytes and took part in osteoarthritis progression ( Li et al, 2019 ). LINC00341 blocked osteoarthritis progression via enhancement of chondrocyte survival ( Yang et al, 2019 ).…”