miR-155 inhibits chondrocyte pyroptosis in knee osteoarthritis by targeting SMAD2 and inhibiting the NLRP3/Caspase-1 pathway

Abstract

Objective Knee osteoarthritis (KOA) is based on degenerative pathological changes. miR-155 is involved in regulating KOA. This study estimated the mechanism of miR-155 in mouse KOA chondrocytes. Methods Mouse KOA chondrocyte model was established by lipopolysaccharide (LPS) induction and identified through Collagen II immunofluorescence staining and toluidine blue staining. LPS-induced KOA chondrocytes were transfected with miR-155 inhibitor or/and si-SMAD2, followed by the evaluation of miR-155 expression, pyroptosis, the SMAD2/NLRP3/Caspase-1 axis-related protein levels, IL-1β and 1L-18 levels, and cell viability by RT-qPCR, FAM-FLICA Caspase-1 Detection Kit, Western blot, ELISA, and MTT assays, respectively. The binding sites between miR-155 and SMAD2 were predicted online and the binding relationship was verified by dual-luciferase assay. Results miR-155 was highly-expressed in LPS-induced KOA chondrocytes. miR-155 knockdown increased cell viability and decreased pyroptotic chondrocytes, and Caspase-1, 1L-1β and 1L-18 levels. miR-155 targeted SMAD2. SMAD2 knockdown partially annulled the effects of miR-155 silencing on inhibiting KOA chondrocyte pyroptosis. NLRP3 pathway was activated in LPS-induced KOA chondrocytes, inhibited after miR-155 knockdown, and activated again after further SMAD2 knockdown. NLRP3 inhibition suppressed Caspase-1, IL-1β, and IL-18 levels and chondrocyte pyroptosis and increased cell viability. Conclusion miR-155 knockdown inhibited the NLRP3/Caspase-1 pathway by targeting SMAD2, thus inhibiting mouse KOA chondrocyte pyroptosis.

miR‐219a‐5p inhibits the pyroptosis in knee osteoarthritis by inactivating the NLRP3 signaling via targeting FBXO3

“…Heretofore, some miRNAs have been found to regulate KOA by mediating pyroptosis, such as miR‐155, which has been researched to be up‐modulated in chondrocytes KOA model. Loss of miR‐155 can mitigate the pyroptosis in chondrocytes KOA model by inhibiting the expression of Caspase‐1, 1L‐1β, and 1L‐18, as well as inactivating the NLRP3 22 . By contrast, miR‐107 expression in chondrocytes KOA model has been implied to be abnormally declined.…”

“…Loss of miR-155 can mitigate the pyroptosis in chondrocytes KOA model by inhibiting the expression of Caspase-1, 1L-1β, and 1L-18, as well as inactivating the NLRP3. 22 By contrast, miR-107 expression in chondrocytes KOA model has been implied to be abnormally declined. Its overmodulation can induce the proliferation of LPS-ATP treated chondrocytes, and repress the expression of Caspase-1, GSDMD, IL-1β and IL-18 in LPS-ATP treated chondrocytes.…”

Recent Therapeutic Strategies for Excessive Chondrocyte Death in Osteoarthritis: A Review

“…Mesenchymal stem cell‐derived exosomes, microRNAs, phytochemical, growth factors, biological enzymes, and exercise all exhibit good potential to inhibit chondrocyte pyroptosis. In addition, inhibitors of pyroptosis‐related pathways have also been shown to alleviate OA by reducing pyroptosis, as seen in Table 4 173–186 …”

“…In addition, inhibitors of pyroptosis-related pathways have also been shown to alleviate OA by reducing pyroptosis, as seen in Table 4. [173][174][175][176][177][178][179][180][181][182][183][184][185][186] Necroptosis N ecrotic apoptosis (necroptosis) refers to a rapid cell death type under extreme physical or chemical stress. The progression and signaling pathways of necroptosis are similar to programmed cell death, which can be triggered by inflammatory mediators, interferon-G, excessive ATP consumption, ischemia-reperfusion injury, and pathogens.…”

Pyroptosis in inflammatory bone diseases: Molecular insights and targeting strategies

“…Herein, we summarize recent studies targeting miRNAs with pyroptosis in inflammatory bone diseases (Table 3). 141–150 …”