Knockdown of lncRNA MFI2-AS1 inhibits lipopolysaccharide-induced osteoarthritis progression by miR-130a-3p/TCF4.
Long noncoding RNA melanotransferrin antisense RNA (MFI2-AS1) plays a vital role in the development of multiple diseases. This study aimed to investigate the effect of this lncRNA on osteoarthritis progression and explore the interaction among MFI2-AS1, microRNA (miR)-130a-3p and transcription factor 4 (TCF4).
Forty-six knee osteoarthritis tissues and 28 normal samples were collected. Human chondrocytes C28/I2 cells treated by lipopolysaccharide (LPS) were used as the model of osteoarthritis. The expression levels of MFI2-AS1, miR-130a-3p and TCF4 were detected by quantitative real-time polymerase chain reaction or western blot. LPS-induced chondrocytes injury was investigated by cell viability, apoptosis, inflammatory response and extracellular matrix degradation using MTT, flow cytometry, enzyme-linked immunosorbent assay and western blot. The target association between miR-130a-3p and MFI2-AS1 or TCF4 was confirmed by luciferase reporter assay and RNA immunoprecipitation.
MFI2-AS1 expression was increased in osteoarthritis tissues and LPS-treated C28/I2 cells. Silence of MFI2-AS1 attenuated LPS-induced viability suppression, apoptosis production, inflammatory response and extracellular matrix degradation. MFI2-AS1 was validated as a decoy of miR-130a-3p and TCF4 was confirmed as a target of miR-130a-3p. miR-130a-3p overexpression inhibited LPS-induced cell injury in C28/I2 cells by decreasing TCF4 expression. Moreover, knockdown of MFI2-AS1 alleviated LPS-induced cell injury in C28/I2 cells by mediating miR-130a-3p and TCF4.
Knockdown of MFI2-AS1 increased cell viability but suppressed apoptosis, inflammatory response and extracellular matrix degradation in LPS-treated chondrocytes by increasing miR-130a-3p and decreasing TCF4, indicating a novel target for the treatment of osteoarthritis.
Luo X
，Wang J
，Wei X
，Wang S
，Wang A
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Blocking HOTAIR protects human chondrocytes against IL-1β-induced cell apoptosis, ECM degradation, inflammatory response and oxidative stress via regulating miR-222-3p/ADAM10 axis.
Long non-coding RNA (lncRNA) HOX transcript antisense RNA (HOTAIR) contributes to cartilage damages including osteoarthritis (OA). While, its role and mechanism in chondrocytes is incompletely clear.
HOTAIR, microRNA (miR)-222-3p and ADAM metalloproteinase-like domain 10 (ADAM10) expressions were detected by real-time quantitative PCR and western blotting. The interaction between miR-222-3p and HOTAIR or ADAM10 was confirmed by dual-luciferase reporter assay. Cell injury was measured by MTS method, flow cytometry, western blotting, enzyme-linked immunosorbent assay for collagen Type II, type X, sex determining region Y-box 9 (SOX9), matrix metalloproteinase (MMP)-13, interleukin (IL)-6, IL-10, and tumor necrosis factor (TNF)-α, and special assay kits for malondialdehyde (MDA), reactive oxygen species (ROS) and superoxide dismutase (SOD).
HOTAIR was highly expressed in human OA cartilages and IL-1β-induced OA model in immortalized chondrocytes (C-28/I2). Under IL-1β stress, blocking HOTAIR was responsible to high mitochondrial activity and low early apoptosis rate, accompanied with increased B cell lymphoma (Bcl)-2 and LC3B-II/I proteins, boosted IL-10 and SOD productions, suppressed cleaved caspase-3 and p62 proteins, and decreased MDA and ROS levels, as well as elevated secretions of Type II collagen, Type X collagen, SOX9, MMP-13, IL-6, and TNF-α. Moreover, miR-222-3p was a target of HOTAIR, and its overexpression and knockdown could suppress and aggravate IL-1β-induced chondrocytes injury. Furthermore, restoring ADAM10, a target gene of miR-222-3p, counteracted the protective role of miR-222-3p upregulation.
HOTAIR might contribute to IL-1β-induced chondrocytes death, inflammation, extracellular matrix degradation, and oxidative stress in OA via miR-222-3p/ADAM10 axis.
Wang J
，Luo X
，Cai S
，Sun J
，Wang S
，Wei X
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Long non-coding RNA PVT1, a molecular sponge for miR-149, contributes aberrant metabolic dysfunction and inflammation in IL-1β-simulated osteoarthritic chondrocytes.
Osteoarthritis (OA), a common form of degenerative joint disease, is typified by inflammatory response and the loss of cartilage matrix. Long non-coding RNAs (lncRNAs) are emerging as a new player in gene regulation and exert critical roles in diverse physiologic and pathogenic processes including OA. The lncRNA plasmacytoma variant translocation 1 (PVT1) has been implicated in cancer, diabetes and septic acute kidney injury. Recent research confirmed the elevation of PVT1 in patients with OA. However, its role in the development of OA remains poorly elucidated. In the present study, high expression of PVT1 was observed in cartilage of OA patients and IL-1β-stimulated chondrocytes. Moreover, cessation of PVT1 expression dramatically reversed the inhibition of IL-1β on collagen II and aggrecan expression, but suppressed IL-1β-induced elevation of matrix metalloproteinases (MMPs), including MMP-3, MMP-9 and MMP-13. Simultaneously, PVT1 inhibition also antagonized the production of inflammatory cytokines upon IL-1β stimulation, including prostaglandin E2 (PGE2), NO, IL-6, IL-8 and TNF-α. Further molecular mechanism analysis identified PVT1 as an endogenous sponge RNA that could directly bind to miR-149 and repress its expression and activity. More importantly, miR-149 inhibition reversed the protective roles of PVT1 cessation in attenuating IL-1β-evoked matrix aberrant catabolism and inflammation. Together, this research confirms that lowering PVT1 expression may ameliorate the progression of OA by alleviating cartilage imbalance toward catabolism and inflammatory response, thus supporting a promising therapeutic strategy against OA.
Zhao Y
，Zhao J
，Guo X
，She J
，Liu Y
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