LncRNA HOTAIR modulates CML cell MDR in a PI3K/Akt-dependent way.
ABSTRACT. This study aimed to investigate the expressional profile of interleukin-6 (IL-6) in articular cartilage bone of osteoarthritis (OA) patients and its correlation with OA. A total of 30 articular cartilage bone samples from knee OA patients, which were collected by knee arthroscopy or articular surgery, comprised the study group, and 30 samples of normal articular cartilage tissue comprised the control group. Both mRNA (messenger ribonucleic acid) and protein levels of IL-6 and matrix metalloproteinase-9 (MMP-9) were measured and compared, and a correlation analysis was performed between the two. The integral optical density (IOD) values of MMP-9 and IL-6 proteins in the study group were 9.21 ± 3.22 and 8.94 ± 3.17, respectively; these were significantly higher (P < 0.05) than those in the control group at 3.14 ± 1.48 and 6.64 ± 1.53, respectively. The IOD values of mRNA transcripts for MMP-9 and IL-6 in the study group were 8.31 ± 2.28 and 8.78 ± 3.43, respectively; these were significantly higher than the values in the control group at 3.52 ± 1.37 and 5.21 ± 1.72 (P < 0.05), respectively. Further, the correlation analysis revealed significantly positive relationships for both protein (r = 0.434, P = 0.001) and mRNA (r = 14190 X.Q. Qu et al.©FUNPEC-RP www.funpecrp.com.br Genetics and Molecular Research 14 (4): 14189-14195 (2015) 0.413, P = 0.002) levels between MMP-9 and IL-6. In conclusion, articular cartilage tissues in knee OA patients have higher levels of MMP-9 and IL-6 expression, and these may play a synergistic role in OA pathogenesis.
Background: Aggrecan plays a crucial role in the ability of tissues to withstand compressive loads during the pathological progression of osteoarthritis (OA). Progressive loss of aggrecan from cartilage may result in exposure of the collagen matrix and can lead to its disintegration by metalloproteases. Although aggrecanases are expressed constitutively in human chondrocytes, the degradation of aggrecan is induced by proinflammatory cytokines; however, little is known about the underlying mechanisms. Methods: Human primary chondrocytes from OA patients or healthy donors and human chondrogenic SW1353 cells were cultured and stimulated with IL-1β in vitro, the mRNA expressions and protein levels of MMP-13, ADAMTS-4, ADAMTS-5, SENP1, and SENP2 were determined using real time PCR and Western blot, respectively. The localizations of aggrecan and Col-II, as well as the SUMOylation modification of these proteins were analyzed using immunofluorescence and immunoprecipitation assays, respectively. Results: Our results showed that a proinflammatory cytokine interleukin-1β induced the OA model and desumoylation of aggrecan and collagen type II because the small ubiquitin-like modifier 2/3 (SUMO2/3) was co-localized with aggrecan and collagen type II proteins and interacted physically with them. Mechanistic studies have shown that knockdown of SUMO2/3 expression can significantly enhance the rate of degradation of aggrecan and collagen type II at both the mRNA and protein levels in the OA model. In addition, SUMO-specific protease 2 (SENP2) plays important roles in the desumoylation of aggrecan, while knockdown of SENP2 can protect aggrecan and collagen type II. Clinical assays have shown that OA patients have higher SENP2 levels than healthy controls, and the SENP2 level correlates negatively with both aggrecan and collagen type II levels. Conclusion: SENP2 desumoylates aggrecan and collagen type II proteins in the inflammation induced OA, and SENP2 expression correlates with OA progression.
Cytokines such as tumor necrosis factor alpha (TNF-α)-induced expression of matrix metalloproteinase (MMP) play a pivotal role in the destruction of articular cartilage in patients who are suffering from osteoarthritis (OA). Collagen type II, the basis for articular cartilage, can be degraded by MMP-1, MMP-3, and 13. EGb761, the standardized extract of Ginkgo biloba produced by Dr. Willar Schwabe Pharmaceuticals, has shown its anti-inflammatory capacity. This study aimed to determine a mechanism whereby EGb761 may inhibit cartilage degradation. Our results indicated that pretreatment with EGb761 abolishes MMP-1, MMP-3, and MMP-13 gene expression and protein expression induced by TNF-α in human chondrocyte monolayer. In addition, the reduction of the tissue inhibitor of metalloproteinase-1(TIMP-1) and metalloproteinase-2 gene expression induced by TNF-α was rescued by pretreatment with EGb761. Importantly, TNF-α-induced degradation of collagen type II was ameliorated by EGb761 in a dose-dependent manner. Mechanistically, our results indicated that EGb761 treatment attenuated TNF-α-induced NF-κB activation. These actions of EGb761 suggest a mechanism by which EGb761 may act to prevent cartilage breakdown in arthritis.
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