Downregulation of Gadd45ß alleviates osteoarthritis by repressing lipopolysaccharide-induced fibroblast-like synoviocyte inflammation, proliferation and migration.

OBJECTIVE: Gadd45ß have a regulatory role in cellular inflammation, proliferation and migration. However, the role of Gadd45ß in synovial inflammation in osteoarthritis (OA) remains to be explored. This study aimed to ascertain whether Gadd45ß is involved in OA synovial inflammation. METHODS: The rat model was induced by sodium iodoacetate and the cellular model was constructed with lipopolysaccharide (LPS)-induced fibroblast-like synoviocytes (FLSs). siRNA was applied to interfere with the expression of intracellular Gadd45ß. Real-time quantitative polymerase chain reaction (RT-qPCR) and western blotting were used to detect the expression of Gadd45ß mRNA and protein. The inflammation, proliferation, and migration of OA-FLSs were detected by enzyme-linked immunosorbent assay, cell scratch assay, 5-ethynyl-2'-deoxyuridine assay, etc. The effect of downregulation of Gadd45ß on the nuclear factor-κB (NF-κB) pathway was investigated. RESULTS: Expression of Gadd45ß in OA rat synovial tissues and OA-FLSs was increased, and LPS treatment promoted cell proliferation and enhanced cell migration. Gadd45ß interference inhibited the inflammation, proliferation and migration of cells induced by LPS. LPS promoted P65 expression in the nucleus and activated the NF-κB signaling pathway, whereas si-Gadd45ß reversed this situation. CONCLUSIONS: si-Gadd45ß inhibited the inflammatory response, proliferation and migration of FLSs, and activation of the NF-κB signaling pathway, which could delay the progression of OA. Hence, it may become a potential therapeutic target for OA.

Diagnostic biomarker panels of osteoarthritis: UPLC-QToF/MS-based serum metabolic profiling.

Osteoarthritis (OA) is the most common joint disease in the world, characterized by pain and loss of joint function, which has led to a serious reduction in the quality of patients' lives. In this work, ultrahigh performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry (UPLC-QToF/MS) in conjunction with multivariate pattern recognition methods and an univariate statistical analysis scheme were applied to explore the serum metabolic signatures within OA group (n = 31), HC (healthy controls) group (n = 57) and non-OA group (n = 19) for early diagnosis and differential diagnosis of OA. Based on logistic regression analysis and receiver operating characteristic (ROC) curve analysis, seven metabolites, including phosphatidylcholine (18:0/22:6), p-cresol sulfate and so on, were identified as critical metabolites for the diagnosis of OA and HC and yielded an area under the curve (AUC) of 0.978. The other panel of unknown m/z 239.091, phosphatidylcholine (18:0/18:0) and phenylalanine were found to distinguish OA from non-OA and achieved an AUC of 0.888. These potential biomarkers are mainly involved in lipid metabolism, glucose metabolism and amino acid metabolism. It is expected to reveal new insight into OA pathogenesis from changed metabolic pathways.

Design and improve of the near-infrared phosphor by adjusting the energy levels or constructing new defects.

Ca3Ga2Ge4O14:Cr3+ phosphors with a broad emission band are prepared by the high temperature solid state method. The emission peak position of Ca3Ga(2-x)Ge4O14:Cr3+ is located at 745 nm. Considering that the biological detection needs a widely spectra matching with the first biological window (650 nm-900 nm), Al3+ and In3+ are introduced into the Ga3+ sites to tune the peak position. When the Ga3+ (0.62 Å) is substituted by smaller Al3+ (0.535 Å), the crystal field around Cr3+ is enhanced, the energy level 4T2(4F) will move up and overlap with 2E(2G) level. As a result, the emission peak of Cr3+shift from 745 nm to 730 nm with an enhancement in the intensity about 19 times due to the electro transfer from 2E(2G) level to 4T2(4F) level. However, the energy level 4T2(4F) will move down when the Ga3+ is replaced by the larger In3+ (0.8 Å), which leads to the red shift of the emission peak from 745 nm to 780 nm. Meanwhile, the intensity is enhanced about 17 times with constructing the defects. In summary, the wide emission spectra of these samples can be tuned from730nm to 780 nm continuously by controlling the concentration of Al3+ and In3+.