Osteopontin Promotes Expression of Matrix Metalloproteinase 13 through NF-<i>κ</i>B Signaling in Osteoarthritis

Li, Yusheng; Jiang, Wei; Wang, Hua; Deng, Zhenhan; Zeng, Chao; Tu, Min; Li, Liangjun; Xiao, Wenfeng; Gao, Shu‐guang; Luo, Wei; Lei, Guanghua

doi:10.1155/2016/6345656

Cited by 19 publications

(18 citation statements)

References 40 publications

(60 reference statements)

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“…Cartilage degeneration is the main feature of OA, and OPN is a secreted multifunctional phosphoprotein involved in the molecular pathogenesis of OA by contributing to progressive degeneration of articular cartilage [11]. In the present study, our results confirmed that the expression of OPN mRNA in human OA cartilage chondrocytes was enhanced compared with that in normal cartilage chondrocytes [7,26].…”

Section: Discussionsupporting

confidence: 84%

The β-catenin/TCF-4 pathway regulates the expression of OPN in human osteoarthritic chondrocytes

Tian

Gao

et al. 2020

Preprint

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Background Cartilage destruction is the main characteristic of osteoarthritis (OA), and osteopontin (OPN) is elevated in OA articular cartilage; however, the reason for the increased OPN level is not determined. In addition, Wnt/β-catenin signaling participates in the progression of OA. The aim of the present study was to evaluate whether canonical Wnt signaling could regulate the expression of OPN in human chondrocytes in vitro. Methods Human chondrocytes were cultured in vitro, and we first assayed the mRNA levels of OPN and β-catenin in chondrocytes. Next, we performed transient transfection of TCF 4 shRNA into chondrocytes to inhibit TCF 4 expression and explore changes in the OPN level. Then, the Wnt/β-catenin signaling inhibitor dinkkopf-1 (Dkk-1) was incubated with chondrocytes, and we assayed the changes in β-catenin and OPN. Results Our results showed that the expression of both β-catenin and OPN was increased in OA chondrocytes, but there were no correlations between β-catenin and OPN expression. TCF4 shRNA downregulated the expression of TCF 4 and OPN in chondrocytes, while after treatment with rDKK-1 at a concentration of 400 ng/ml for 24 h, the mRNA and protein expression of both β-catenin and OPN was significantly decreased in chondrocytes. Conclusions Elevated OPN expression might be regulated by the β-catenin/TCF-4 pathway, and the Wnt/β-catenin inhibitor DKK1 could inhibit the expression of β-catenin and OPN in OA chondrocytes.

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Section: Discussionsupporting

confidence: 84%

The β-catenin/TCF-4 pathway regulates the expression of OPN in human osteoarthritic chondrocytes

Tian

Gao

et al. 2020

Preprint

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“…Interestingly, mRNA expression and protein abundance of OPN are associated with the pathogenesis of OA [42]. Pullig et al had demonstrated that the SPP1 mRNA isolated from human OA cartilage is elevated compared to normal cartilage samples [46].…”

Section: Impact Of Vibration On Osteopontinmentioning

confidence: 99%

Pathway Analysis Hints Towards Beneficial Effects of Long-Term Vibration on Human Chondrocytes

Lützenberg

Solano

Buken

et al. 2018

Cell Physiol Biochem

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Background/Aims: Spaceflight negatively influences the function of cartilage tissue in vivo. In vitro human chondrocytes exhibit an altered gene expression of inflammation markers after a two-hour exposure to vibration. Little is known about the impact of long-term vibration on chondrocytes. Methods: Human cartilage cells were exposed for up to 24 h (VIB) on a specialised vibration platform (Vibraplex) simulating the vibration profile which occurs during parabolic flights and compared to static control conditions (CON). Afterwards, they were investigated by phase-contrast microscopy, rhodamine phalloidin staining, microarray analysis, qPCR and western blot analysis. Results: Morphological investigations revealed no changes between CON and VIB chondrocytes. F-Actin staining showed no alterations of the cytoskeleton in VIB compared with CON cells. DAPI and TUNEL staining did not identify apoptotic cells. ICAM-1 was elevated and vimentin, beta-tubulin and osteopontin proteins were significantly reduced in VIB compared to CON cells. qPCR of cytoskeletal genes, ITGB1, SOX3, SOX5, SOX9 did not reveal differential regulations. Microarray analysis detected 13 differentially expressed genes, mostly indicating unspecific stimulations. Pathway analyses demonstrated interactions of PSMD4 and CNOT7 with ICAM. Conclusions: Long-term vibration did not damage human chondrocytes in vitro. The reduction of osteopontin protein and the down-regulation of PSMD4 and TBX15 gene expression suggest that in vitro long-term vibration might even positively influence cultured chondrocytes.

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“…Adipose tissue of obese individuals produces elevated amounts of numerous mediators of inflammation [ 70 , 71 , 72 ]. Articular cartilage matrix tissue destruction by metalloproteinases, observed in OA, may result from chronic activation of obesity-induced pro-inflammatory intracellular signaling in joints [ 73 , 74 , 75 ]. A set of clinical studies demonstrated curcumin, curcuminoid, and curcumin-based therapeutics to improve the extremity function and reduce pain and treatment in OA patients [ 76 , 77 , 78 , 79 ].…”

Section: Discussionmentioning

confidence: 99%

Effects of Curcumin in a Mouse Model of Very High Fat Diet-Induced Obesity

et al. 2020

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Worldwide rates of Western-diet-induced obesity epidemics are growing dramatically. Being linked with numerous comorbidities and complications, including cardiovascular disease, type 2 diabetes, cancer, chronic inflammation, and osteoarthritis (OA), obesity represents one of the most threatening challenges for modern healthcare. Mouse models are an invaluable tool for investigating the effects of diets and their bioactive components against high fat diet (HFD)-induced obesity and its comorbidities. During recent years, very high fat diets (VHFDs), providing 58–60% kcal fat, have become a popular alternative to more traditional HFDs, providing 40–45% total kcal fat, due to the faster induction of obesity and stronger metabolic responses. This project aims to investigate if the 60% fat VHFD is suitable to evaluate the protective effects of curcumin in diet-induced obesity and osteoarthritis. B6 male mice, prone to diet-induced metabolic dysfunction, were supplemented with VHFD without or with curcumin for 13 weeks. Under these experimental conditions, feeding mice a VHFD for 13 weeks did not result in expected robust manifestations of the targeted pathophysiologic conditions. Supplementing the diet with curcumin, in turn, protected the animals against obesity without significant changes in white adipocyte size, glucose clearance, and knee cartilage integrity. Additional research is needed to optimize diet composition, curcumin dosage, and duration of dietary interventions to establish the VHFD-induced obesity for evaluating the effects of curcumin on metabolic dysfunctions related to obesity and osteoarthritis.

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Osteopontin Promotes Expression of Matrix Metalloproteinase 13 through NF-κB Signaling in Osteoarthritis

Cited by 19 publications

References 40 publications

The β-catenin/TCF-4 pathway regulates the expression of OPN in human osteoarthritic chondrocytes

The β-catenin/TCF-4 pathway regulates the expression of OPN in human osteoarthritic chondrocytes

Pathway Analysis Hints Towards Beneficial Effects of Long-Term Vibration on Human Chondrocytes

Effects of Curcumin in a Mouse Model of Very High Fat Diet-Induced Obesity

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