Glycoproteins are involved in the development of many diseases, while the type and content of N-glycoproteins in the cartilage of osteoarthritis (OA) and Kashin–Beck disease (KBD) are still unclear. This research aims to identify N-glycoproteins in knee cartilage patients with OA and KBD compared with normal control (N) adults. The cartilage samples were collected from gender- and age-matched OA (n = 9), KBD (n = 9) patients, and N (n = 9) adults. Glycoproteomics and label-free liquid chromatography-tandem mass spectrometry (LC-MS/MS) obtained N-glycoproteins of KBD and OA. A total of 594 N-glycoproteins and 1146 N-glycosylation peptides were identified. The identified data were further compared and analyzed with Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Protein–Protein Interactions (PPI). Pairwise comparison of the glycoproteins detected in the three groups showed that integrin beta-1 (ITGB1), collagen alpha-1 (II) chain (COL2A1), collagen alpha-1 (VII) chain (COL7A1), carbohydrate sulfotransferase 3 (CHST-3), carbohydrate sulfotransferase 4 (CHST-4), thrombospondin 2 (THBS2), bone morphogenetic protein 8A (BMP8A), tenascin-C (TNC), lysosome-associated membrane protein (LAMP2), and beta-glucuronidase (GUSB) were significantly differentially expressed. GO results suggested N-glycoproteins mainly belonged to protein metabolic process, single-multicellular and multicellular organism process, cell adhesion, biological adhesion, and multicellular organism development. KEGG and PPI results revealed that key N-glycoproteins were closely related to pathways for OA and KBD, such as phagosome, ECM-receptor interaction, lysosome, focal adhesion, protein digestion, and absorption. These results reflected glycoprotein expression for OA and KBD in the process of ECM degradation, material transport, cell–cell or cell–ECM interaction, and information transduction. These key significantly differentially expressed N-glycoproteins and pathways lead to the degeneration and degradation of the cartilage of OA and KBD mainly by disrupting the synthesis and catabolism of basic components of ECM and chondrocytes and interfering with the transfer of material or information. The key N-glycoproteins or pathways in this research are potential targets for pathological mechanisms and therapies of OA and KBD.

https://www.mdpi.com/2073-4409/11/16/2513/pdf?version=1660870911

Identification of N-Glycoproteins of Knee Cartilage from Adult Osteoarthritis and Kashin-Beck Disease Based on Quantitative Glycoproteomics, Compared with Normal Control Cartilage

YAP plays a protective role in T-2 toxin-induced inhibition of chondrocyte proliferation and matrix degradation

Fluoride Exposure Provokes Mitochondria-Mediated Apoptosis and Increases Mitophagy in Osteocytes via Increasing ROS Production

Objective To explore the function and mechanism of Sirt-1 in fluorine-induced liver injury. Method Fluorosis rats were first established. The fluorine content, pathological structure, collagen fibers, and fibrosis in liver tissues were tested through the fluoride ion selective electrode method, H&E, Masson, and Sirius red staining; alanine aminotransferase (ALT), aspartate aminotransferase (AST), interleukin 18 (IL-18), and tumor necrosis factor-α (TNF-α) levels in rat serum were also analyzed using ELISA kits. Then, the fluorosis cell model was built, which was also alleviated with NaF, Sirt-1 siRNAs, or endoplasmic reticulum stress (ERS) alleviator (4-PBA). CCK-8 also assessed cell proliferation; RT-qPCR or Western blots detect sirtuin-1 (Sirt-1), protein kinase R- (PKR-) like endoplasmic reticulum kinase (PERK), and endoplasmic reticulum stress (ERS) and apoptosis-related protein levels in liver tissue. Results Our results uncovered that fluorine exposure could aggravate the pathological damage and fibrosis of rat liver tissues and increase indicators related to liver injury. And fluoride exposure also could downregulate Sirt-1 and upregulate ERS-related proteins (PERK, 78-kD glucose-regulated protein (GRP-78), and activating transcription factor 6 (ATF6)) and apoptosis-related protein (caspase-3 and C/EBP-homologous protein (CHOP)) in rat liver tissues. Besides, we proved that fluoride exposure could suppress proliferation and enhances ERS and apoptotic pathways in AML12 cells by downregulating Sirt-1. Moreover, we revealed that ERS alleviator (4-PBA) could induce proliferation and prevent ERS and apoptosis in fluorine-exposed AML12 cells. Conclusions We suggested that fluorine exposure can induce hepatocyte ERS and apoptosis through downregulation of Sirt-1.

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Fluoride Exposure Suppresses Proliferation and Enhances Endoplasmic Reticulum Stress and Apoptosis Pathways in Hepatocytes by Downregulating Sirtuin-1

Abstract Fluoride, one of the global groundwater contaminants, is ubiquitous in our day-to-day life from various natural and anthropogenic sources. Numerous in vitro, in vivo, and epidemiological studies are conducted to understand the effect of fluoride on biological systems. A low concentration of fluoride is reported to increase oral health, whereas chronic exposure to higher concentrations causes fluoride toxicity (fluorosis). It includes dental fluorosis, skeletal fluorosis, and fluoride toxicity in soft tissues. The mechanism of fluoride toxicity has been reviewed extensively. However, epigenetic regulation in fluoride toxicity has not been reviewed. This systematic review summarizes the current knowledge regarding fluoride-induced epigenetic toxicity in the in vitro, in vivo, and epidemiological studies in mammalian systems. We examined four databases for the association between epigenetics and fluoride exposure. Out of 932 articles (as of 31 March 2022), 39 met our inclusion criteria. Most of the studies focused on different genes, and overall, preliminary evidence for epigenetic regulation of fluoride toxicity was identified. We further highlight the need for epigenome studies rather than candidate genes and provide recommendations for future research. Our results indicate a correlation between fluoride exposure and epigenetic processes. Further studies are warranted to elucidate and confirm the mechanism of epigenetic alterations mediated fluoride toxicity.

A systematic review on fluoride-induced epigenetic toxicity in mammals

Fluorine is widely dispersed in nature and has multiple physiological functions. Although it is usually regarded as an essential trace element for humans, this view is not held universally. Moreover, chronic fluorosis, mainly characterized by skeletal fluorosis, can be induced by long-term excessive fluoride consumption. High concentrations of fluoride in the environment and drinking water are major causes, and patients with skeletal fluorosis mainly present with symptoms of osteosclerosis, osteochondrosis, osteoporosis, and degenerative changes in joint cartilage. Etiologies for skeletal fluorosis have been established, but the specific pathogenesis is inconclusive. Currently, active osteogenesis and accelerated bone turnover are considered critical processes in the progression of skeletal fluorosis. In recent years, researchers have conducted extensive studies in fields of signaling pathways (Wnt/β-catenin, Notch, PI3K/Akt/mTOR, Hedgehog, parathyroid hormone, and insulin signaling pathways), stress pathways (oxidative stress and endoplasmic reticulum stress pathways), epigenetics (DNA methylation and non-coding RNAs), and their inter-regulation involved in the pathogenesis of skeletal fluorosis. In this review, we summarised and analyzed relevant findings to provide a basis for comprehensive understandings of the pathogenesis of skeletal fluorosis and hopefully propose more effective prevention and therapeutic strategies.

Progress of Signaling Pathways, Stress Pathways and Epigenetics in the Pathogenesis of Skeletal Fluorosis.

ObjectiveTo investigate the effects of low nutrition and trichothecenes-2 toxin (T-2) on human chondrocytes cell line C28/I2 and the gene expression levels of some chondroitin sulfate (CS)–modifyin...

Effect of Low Nutrition and T-2 Toxin on C28/I2 Chondrocytes Cell Line and Chondroitin Sulfate-Modifying Sulfotransferases.

ObjectiveTo investigate the protective effect of chondroitin sulfate nano-selenium (SeCS) on chondrocyte of Kashin-Beck disease (KBD).MethodsChondrocyte samples were isolated from the cartilage of ...

Lichun Qiao

Papers

Progress of Signaling Pathways, Stress Pathways and Epigenetics in the Pathogenesis of Skeletal Fluorosis.

Effect of Low Nutrition and T-2 Toxin on C28/I2 Chondrocytes Cell Line and Chondroitin Sulfate-Modifying Sulfotransferases.

Protective effect of chondroitin sulfate nano-selenium on chondrocyte of patients with Kashin-Beck disease.