Subversive molecular role of Krüppel-like factor 5 in extracellular matrix degradation and chondrocyte dedifferentiation.

Osteoarthritis (OA) is the most common joint disorder worldwide and a leading cause of pain and disability. However, the pathogenesis of osteoarthritis has not been elucidated. Krüppel-like factor (KLF)-5 is involved in several biological processes, including inflammation and cell differentiation, but its role in OA has not been evaluated.

Novel 1,3,4-oxadiazole compounds inhibit the tyrosinase and melanin level: Synthesis, in-vitro, and in-silico studies.

In this research work, we have designed and synthesized some biologically useful of 1,3,4-Oxadiazoles. The structural interpretation of the synthesized compounds has been validated by using FT-IR, LC-MS, HRMS, H NMR and C NMR techniques. Moreover, the in-vitro mushroom tyrosinase inhibitory potential of the target compounds was assessed.

Simvastatin abolishes nitric oxide- and reactive oxygen species-induced cyclooxygenase-2 expression by blocking the nuclear factor κB pathway in rabbit articular chondrocytes.

Nitric oxide (NO) and reactive oxygen species (ROS) have been shown to be linked with numerous diseases, including osteoarthritis (OA). Our study aimed to examine the effect of simvastatin on NO- or ROS-induced cyclooxygenase-2 (COX-2) expression in OA. Simvastatin has attracted considerable attention since the discovery of its pharmacological effects on different pathogenic processes, including inflammation.

Inhibitory effects on melanogenesis by thymoquinone are mediated through the β‑catenin pathway in B16F10 mouse melanoma cells.

Thymoquinone (TQ) is a component found in the seeds of Nigella sativa, an annual plant growing on the Mediterranean coast, and is known for its anticancer and anti‑inflammatory effects. However, to date, at least to the best of our knowledge, limited studies are available examining the molecular mechanisms through which TQ inhibits melanogenesis. Accordingly, this study aimed to treat B16F10 mouse melanoma cells with TQ to investigate its apparent effects and its molecular regulatory mechanisms.

Gallotannin attenuates 2‑deoxy‑D‑glucose‑induced dedifferentiation and endoplasmic reticulum stress through inhibition of inositol‑requiring enzyme 1 downstream p38 kinase pathway in chondrocytes.

Gallotannin (GT) is a class of polyphenols with antioxidant, anticancer, and antiviral activities. 2‑Deoxy‑D‑glucose (2DG), a glucose‑derived molecule, can inhibit glucose metabolism and induce endoplasmic reticulum (ER) stress. GT in primary‑cultured chondrocytes enhances expression of type II collagen, an indicator of differentiation, and cyclooxygenase‑2 (COX‑2), which mediates inflammatory reactions.

Simvastatin induces differentiation in rabbit articular chondrocytes via Wnt/β-catenin pathway.

Simvastatin is widely used as a specific inhibitor of 3-hydroxy-3-methyl-glutaryl-CoA reductase to reduce the levels of low-density lipoprotein cholesterol. However, its regulatory mechanism in chondrocyte differentiation is unclear. This study was conducted to evaluate the effects and signalling pathway of simvastatin on chondrocyte differentiation.

Synthesis and exploration of a novel chlorobenzylated 2-aminothiazole-phenyltriazole hybrid as migratory inhibitor of B16F10 in melanoma cells.

In the study presented here, a novel chlorobenzylated bi-heterocyclic hybrid molecule () was synthesized and its structural confirmation was carried out by IR, H-NMR, C-NMR and CHN analysis data. This compound was subjected to biological study with B16F10 mouse melanoma cells. The anti-proliferative results showed that showed no significant toxicity at concentrations ranging of 0-44 μM.

Simvastatin prevents articular chondrocyte dedifferentiation induced by nitric oxide by inhibiting the expression of matrix metalloproteinases 1 and 13.

Dedifferentiation of chondrocytes is the main character of cartilage degradation. Therefore the understanding of chondrocytes dedifferentiation is essential for arthritis therapy. However, the molecular mechanism of cartilage destroy is mostly unknown.

Kruppel-like factor 4 (KLF-4) plays a crucial role in simvastatin (SVT)-induced differentiation of rabbit articular chondrocytes.

Simvastatin is a cholesterol-lowing reagent that is derived synthetically from the fermentation of Aspergillus terreus. Recently, SVT has been shown to possess a protective effect of chondrocytes. Kruppel-like factor 4 (KLF-4) is a zinc finger transcription factor that plays crucial roles during the development and maintenance of multiple organs.

PEP-1-glutaredoxin-1 induces dedifferentiation of rabbit articular chondrocytes by the endoplasmic reticulum stress-dependent ERK-1/2 pathway and the endoplasmic reticulum stress-independent p38 kinase and PI-3 kinase pathways.

Glutaredoxin-1 (GRX-1), belonging to the oxidoreductase family, is a component of the endogenous antioxidant defense system. In this study, we evaluated the effects of PEP-1-GRX-1 in rabbit articular chondrocytes. We found that PEP-1-GRX-1 causes a loss of the differentiated chondrocyte phenotype.

Cytokine-induced apoptosis inhibitor-1 causes dedifferentiation of rabbit articular chondrocytes via the ERK-1/2 and p38 kinase pathways.

Cytokine-induced apoptosis inhibitor-1 (CIAPIN-1, formally named anamorsin) is a well-known regulator of apoptosis in many different cell types. Recently, it has been reported that some anti-apoptotic proteins are involved with the regulation of cell differentiation. However, relatively little is known about the role of CIAPIN-1 on rabbit articular chondrocytes differentiation.

5-Azacytidine regulates matrix metalloproteinase-9 expression, and the migration and invasion of human fibrosarcoma HT1080 cells via PI3-kinase and ERK1/2 pathways.

Abnormal methylation of promoter CpG islands is one of the hallmarks of cancer cells, and is catalyzed by DNA methyltransferases. 5-azacytidine (5-aza C), a methyltransferase inhibitor, can cause demethylation of promoter regions of diverse genes. Epigenetic processes contribute to the regulation of matrix metalloproteinase (MMP) expression.

Salinomycin causes migration and invasion of human fibrosarcoma cells by inducing MMP-2 expression via PI3-kinase, ERK-1/2 and p38 kinase pathways.

Salinomycin (SAL) is a polyether ionophore antibiotic that has recently been shown to regulate a variety of cellular responses in various human cancer cells. However, the effects of SAL on metastatic capacity of HT1080 human fibrosarcoma cells have not been elucidated. We investigated the effect of SAL on migration and invasion, with emphasis on the expression and activation of matrix metalloproteinase (MMP)-2 in HT1080 human fibrosarcoma cells.

Berberine induces dedifferentiation by actin cytoskeleton reorganization via phosphoinositide 3-kinase/Akt and p38 kinase pathways in rabbit articular chondrocytes.

Osteoarthritis is a nonrheumatologic joint disease characterized by progressive degeneration of the cartilage extracellular matrix. Berberine (BBR) is an isoquinoline alkaloid used in traditional Chinese medicine, the majority of which is extracted from Huang Lian (Coptis chinensis). Although numerous studies have revealed the anticancer activity of BBR, its effects on normal cells, such as chondrocytes, and the molecular mechanisms underlying its actions remain elusive.

DNA-hypomethylating agent, 5'-azacytidine, induces cyclooxygenase-2 expression via the PI3-kinase/Akt and extracellular signal-regulated kinase-1/2 pathways in human HT1080 fibrosarcoma cells.

The cytosine analogue 5'-azacytidine (5'-aza) induces DNA hypomethylation by inhibiting DNA methyltransferase. In clinical trials, 5'-aza is widely used in epigenetic anticancer treatments. Accumulated evidence shows that cyclooxygenase-2 (COX-2) is overexpressed in various cancers, indicating that it may play a critical role in carcinogenesis.

Salinomycin causes dedifferentiation via the extracellular signal-regulated kinase (ERK) pathway in rabbit articular chondrocytes.

Salinomycin (SAL), a monocarboxylic polyether antibiotic isolated from Streptomyces albus, modulates various cellular responses, including proliferation, apoptosis, and inflammation. However, the effect of SAL on the dedifferentiation of chondrocytes remains unclear. Thus, we investigated the effects and regulatory mechanisms of SAL on the dedifferentiation of rabbit articular chondrocytes.

The thymoquinone-induced production of reactive oxygen species promotes dedifferentiation through the ERK pathway and inflammation through the p38 and PI3K pathways in rabbit articular chondrocytes.

Dedifferentiation and inflammation are major features of cartilage degeneration during the pathogenesis of osteoarthritis (OA). Thymoquinone (TQ) is the major compound of black seed oil isolated from Nigella sativa with various beneficial or harmful effects on several diseases; however, its effects on the dedifferentiation and inflammation of chondrocytes have not yet been characterized. In the present study, we investigated whether TQ regulates the dedifferentiation and inflammation of rabbit articular chondrocytes, focusing on the production of reactive oxygen species (ROS) in rabbit articular chondrocytes.

Withaferin A-caused production of intracellular reactive oxygen species modulates apoptosis via PI3K/Akt and JNKinase in rabbit articular chondrocytes.

Withaferin A (WFA) is known as a constituent of Ayurvedic medicinal plant, Withania somnifera, and has been used for thousands of years. Although WFA has been used for the treatment of osteoarthritis (OA) and has a wide range of biochemical and pharmacologic activities, there are no findings suggesting its properties on chondrocytes or cartilage. The aim of the present study is to investigate the effects of WFA on apoptosis with focus on generation of intracellular reactive oxygen species (ROS).

Synthesis, crystal structure, anti-inflammatory and anti-hyperglycemic activities of novel 3,4-disubstituted 1,2,4-triazol-5(4H)-one derivatives.

A new series of 3,4-disubstituted 1,2,4-triazol-5(4H)-one 5a-r, bearing various methoxyphenyl, fluorophenyl, tolyl and phenyl groups, was synthesized by the dehydrocyclization of hydrazinecarboxamides 4a-r by refluxing in a 2 N sodium hydroxide solution. Hydrazinecarboxamides 4a-r was synthesized via the condensation of the corresponding aralkanoic acid hydrazides, 3a-g, with fluoro-, tolyl- and methoxyphenylisocyanates. The newly synthesized compounds (5a-r) were characterized by IR, (1)H NMR and (13)C NMR analyses.

Production of reactive oxygen species by withaferin A causes loss of type collagen expression and COX-2 expression through the PI3K/Akt, p38, and JNK pathways in rabbit articular chondrocytes.

Withaferin A (WFA) is a major chemical constituent of Withania somnifera, also known as Indian ginseng. Many recent reports have provided evidence of its anti-tumor, anti-inflammation, anti-oxidant, and immune modulatory activities. Although the compound appears to have a large number of effects, its defined mechanisms of action have not yet been determined.

Thymoquinone-induced reactive oxygen species causes apoptosis of chondrocytes via PI3K/Akt and p38kinase pathway.

Thymoquinone (TQ), a bioactive ingredient of the volatile oil of black seed (Nigella sativa), has been shown to possess anti-neoplastic and anti-inflammatory effects on a variety of tumours. However, the precise mechanism of action is not clear in normal cells such as primary chondrocytes. So, we have investigated the effects of TQ on the apoptosis of chondrocytes with a focus on reactive oxygen species (ROS) production.

Sulforaphane inhibits proliferation by causing cell cycle arrest at the G2/M phase in rabbit articular chondrocytes.

Sulforaphane (SFN), a natural compound extracted from cruciferous vegetables, exhibits potent anticancer activity in various types of tumor cells. However, the effect of SFN on the proliferation of chondrocytes is not well understood. In the present study, we addressed the mechanism of action by which SFN suppresses proliferation.

Protein phosphorylation on tyrosine restores expression and glycosylation of cyclooxygenase-2 by 2-deoxy-D-glucose-caused endoplasmic reticulum stress in rabbit articular chondrocyte.

2-deoxy-D-glucose(2DG)-caused endoplasmic reticulum (ER) stress inhibits protein phosphorylation at tyrosine residues. However, the accurate regulatory mechanisms, which determine the inflammatory response of chondrocytes to ER stress via protein tyrosine phosphorylation, have not been systematically evaluated. Thus, in this study, we examined whether protein phosphorylation at tyrosine residues can modulate the expression and glycosylation of COX-2, which is reduced by 2DG-induced ER stress.

Endoplasmic reticulum stress (ER-stress) by 2-deoxy-D-glucose (2DG) reduces cyclooxygenase-2 (COX-2) expression and N-glycosylation and induces a loss of COX-2 activity via a Src kinase-dependent pathway in rabbit articular chondrocytes.

Endoplasmic reticulum (ER) stress regulates a wide range of cellular responses including apoptosis, proliferation, inflammation, and differentiation in mammalian cells. In this study, we observed the role of 2-deoxy-D-glucose (2DG) on inflammation of chondrocytes. 2DG is well known as an inducer of ER stress, via inhibition of glycolysis and glycosylation.

2-Deoxy-D-glucose regulates dedifferentiation through beta-catenin pathway in rabbit articular chondrocytes.

2-deoxy-D-glucose (2DG) is known as a synthetic inhibitor of glucose. 2DG regulates various cellular responses including proliferation, apoptosis and differentiation by regulation of glucose metabolism in cancer cells. However, the effects of 2DG in normal cells, including chondrocytes, are not clear yet.