We also evaluated SREBP-2, its target gene 3-hydroxy-3-methylglutaryl-coenzymeA reductase (HMGCR), phospho-phosphoinositide3-kinase (PI3K), phospho-Akt, integrin-alphaV (ITGAV) and transforming growth factor-β (TGF-β) mRNA and protein expression levels in osteoarthritic and normal chondrocytes and found that they were all significantly elevated in OA chondrocytes.
Using quantitative PCR and Western blot analysis, we found that PI3Kδ mRNA and protein expression is higher in RA than in osteoarthritis (OA) synovium.
Urolithin A targets the PI3K/Akt/NF-κB pathways and prevents IL-1β-induced inflammatory response in human osteoarthritis: in vitro and in vivo studies.
Transcriptional profiling of 4-ABP-stimulated MSC suggested that <i>RPS6KA2</i> and the PI3K-Akt pathway were 4-ABP targets; 4-ABP could activate the PI3K-Akt pathway to promote MSC proliferation and repair OA injury, which was blocked in <i>RPS6KA2-</i>knockdown MSC or <i>RPS6KA2-</i>deficient mice<i>.</i><b>Conclusion</b> 4-ABP bio-distribution in cartilage promotes proliferation and chondrogenic differentiation of MSC, and repairs osteoarthritic lesions via PI3K-Akt pathway activation.
Together, this research suggested that CTRP3 might protect chondrocytes against IL-1β-induced injury by suppressing the FGFR1- Ras/PI3K/Akt signaling-mediated growth inhibitory pathway, indicating a potential agent against osteoarthritis.
These results show that MALAT1 can modulate ECM catabolism, inflammation, and especially apoptosis in chondrocytes treated with LPS, which targets PI3K/Akt/mTOR to eventually regulate the progression of OA.
Therefore, the data suggested that miR-634 could suppress survival and matrix synthesis of high grade OA chondrocytes through targeting PIK3R1 gene to modulate the PI3K/Akt/S6 and PI3K/Akt/mTOR/S6 axes, with important implication for validating miR-634 as a potential target for OA therapy.
Targeting MALAT1 so as to rescue miR-127-5p expression in OA might help to inhibit chondrocyte proliferation through miR-127-5p-mediated OPN regulation and downstream PI3K/Akt pathway..
Taken together, our data first demonstrated that myricetin possesses the therapeutic potential on OA through PI3K/Akt mediated Nrf2/HO-1 signaling pathway.
Results also indicated that JEZTC exerts effect on OA by regulating MAPKs and PI3K/Akt signaling pathways to activate NF-κB pathway, leading to the down-regulation of MMPs.
Primary human OA osteoblasts were treated with ET‑1 (1, 5, 10, 20 and 30 nM) for 0.5, 1, 2, 3 and 4 h with or without the selective ETA receptor (ETAR) antagonist, BQ123, ETB receptor antagonist, BQ788 or the phosphatidylinositol 3‑kinase (PI3K) inhibitor, BKM120.
miR-4262 regulates chondrocyte viability, apoptosis, autophagy by targeting SIRT1 and activating PI3K/AKT/mTOR signaling pathway in rats with osteoarthritis.
MATERIAL AND METHODS To clarify the roles of loganin in OA and its specific signaling pathway, chondrocytes were administrated with IL-1ß and supplemented with or without LY294002 (a classic PI3K/Akt inhibitor).
Inhibition of PI3K/AKT/mTOR signaling pathway could promote the autophagy of articular chondrocytes and attenuate inflammation response in rats with OA.
In addition, osteoclast differentiation, FoxO, MAPK and PI3K/Akt signaling pathways were revealed to be imperative for the pathogenesis of OA, as these 4 pivotal signaling pathways were observed to be tightly linked through 4 key TFs Fos Proto-Oncogene, JUN, JunD Proto-Oncogene and MYC, and 4 DEGs Vascular Endothelial Growth Factor A, Growth Arrest and DNA Damage Inducible α, Growth Arrest and DNA Damage Inducible β and Cyclin D1.
Here, a mouse destabilization OA model in the tibia was used to investigate roles of PI3K/AKT signaling in the early subchondral bone changes and OA pathological process.