Nuclear receptors regulate lipid metabolism and oxidative stress markers in chondrocytes

Ratneswaran, A.; Sun, Margaret Man-Ger; Dupuis, Holly; Sawyez, Cynthia G.; Borradaile, Nica M.; Beier, Frank

doi:10.1007/s00109-016-1501-5

Cited by 37 publications

(45 citation statements)

References 53 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…It is the only known chemokine that can bind to and activate C-X-C motif chemokine receptor4 (CXCR4) on the surface of chondrocyte. The combination of the two can form a coupled molecular pair that is closely related to the transmission of information between cells and cell migration (14) . Exogenous chemokines from the synovium and bone marrow belong to the C-X-C chemokine subfamily, which is a very strong inducer of cartilage matrix degradation.…”

Section: Resultsmentioning

confidence: 99%

Guyanxiao formula antagonizes LPS-induced KOA chondrocyte injury by regulating the SDF-1 / CXCR4 signaling pathway1

Zhang

Shu-guang

Wang

et al. 2020

Preprint

View full text Add to dashboard Cite

Background To determine whether Guyanxiao formula protects chondrocytes in a model of knee arthritis induced by lipopolysaccharide, and whether it can repair chondrocyte damage and suppress osteoarthritis cartilage degeneration by regulating SDF-1 / CXCR4 signaling pathway.Methods Lipopolysaccharide(LPS) induces chondrocytes in vitro to prepare knee osteoarthritis model. Toluidine blue (TBS) staining was used to observe the changes of proteoglycan content of rabbit chondrocytes in order to identify the source of cells. The biochemical detection method was used to determine the content of inflammatory factor nitric oxide (NO) in chondrocytes to identify whether the osteoarthritis chondrocytes were successfully modeled in vitro.The cell proliferation rate was measured by the cell viability test (CCK-8), the concentration with no obvious cytotoxicity was screened, and the low, medium and high dose groups of Guyanxiao formula were established.Immunofluorescence(IF) staining was used to observe the effect of Guyanxiao formula on the content of type Ⅱ collagen in chondrocytes of knee osteoarthritis.Enzyme-linked immunosorbent assay was carried out to determine the expression of inflammatory factors MMP-3, MMP-9 and MMP-13. The mRNA and protein expressions of SDF-1, CXCR4, Vascular endothelial growth factor(VEGF) were analyzed by reverse transcription quantitative polymerase chain reaction and Western blot analysis.Results The identify of chondrocytes was confirmed with toluidine blue staining. LPS treatment remarkably increased the NO content, indicating successful noodling of the KOA chondrocyte model. According to the CCK-8 experiment results, 0.36, 3.6, and 36 µg / mL were set as the low, medium, and high dose administration concentrations of ostitis.Immunofluorescence(IF) staining showed that the degree of type Ⅱ collagen damage in each treatment group was improved compared with the model group, and the high concentration group was the most obvious improvement in the Guyanxiao formula treatment group.The levels of MMP-3,MMP-9, MMP-13, and IL-1b were much lower in the Cell supernatant of the each treatment group than in that of model group.The levels of SDF-1, CXCR4, VEGF mRNA and protein were much lower in the Chondrocytes of the each treatment group than in that of model group. In addition, the therapeutic effect of Guyanxiao formula treatment group decreased in a concentration-dependent manner.Conclusion Guyanxiao formula antagonizes LPS-induced KOA chondrocyte injury by regulating the SDF-1 / CXCR4 signaling pathway.

show abstract

Section: Resultsmentioning

confidence: 99%

Guyanxiao formula antagonizes LPS-induced KOA chondrocyte injury by regulating the SDF-1 / CXCR4 signaling pathway1

Zhang

Shu-guang

Wang

et al. 2020

Preprint

View full text Add to dashboard Cite

show abstract

“…This could be due to cell type-specific effects, but changes in experimental design could also contribute to these differences. In particular, growth plate chondrocytes were incubated with GW3965 for 24 hours, while IMACs received the drug for 72 hours (19). Thus, secondary or tertiary effects of LXR activation would only be seen in the IMAC system.…”

Section: Discussionmentioning

confidence: 99%

“…Total RNA (200 ng/uL) from three independent cell culture experiments underwent 2 rounds of amplifications, then labeling and hybridization to Affymetrix GeneChip™ Mouse Gene 2.0 ST Array (Thermo Fisher Scientific) containing probe sets representing > 28,000 coding transcripts, as previously described (19). The complete microarray data set will be deposited at the publicly accessible Gene Expression Omnibus (GEO) database, and NCBI accession number provided.…”

Section: Methodsmentioning

confidence: 99%

“…A subset of RNA isolated from E15.5 primary chondrocytes was used for gene expression analysis through real-time quantitative PCR, as previously described (19,23,25). Complimentary DNA (cDNA) synthesis was conducted using the iScript™ cDNA Synthesis Kit with 500 ng of starting RNA (Bio-Rad Laboratories), and combined with 50 μM of forward and reverse primers (for primer sequences, please see Supplementary Table 1) as well as iQ™ SYBR ® Green Supermix (Bio-Rad Laboratories).…”

Section: Methodsmentioning

confidence: 99%

“…At the end of the 6-day incubation period, tibiae were rinsed with phosphate-buffered saline (PBS) and fixed overnight with 4% paraformaldehyde (PFA) (Sigma-Aldrich), then embedded and sectioned at the Molecular Pathology Core Facility, Robarts Institute (London, ON, Canada). Immunohistochemistry was conducted as described with minor modifications (19,23). Paraffin sections were dewaxed and carried through a series of rehydration steps, followed by incubation in 3% H 2 O 2 .…”

Section: Methodsmentioning

confidence: 99%

See 2 more Smart Citations

Liver X Receptor activation regulates genes involved in lipid homeostasis in developing chondrocytes

Sun

Beier

2019

Preprint

Self Cite

View full text Add to dashboard Cite

23Objective: Osteoarthritis (OA) is the most common type of arthritis and causes debilitating 24 symptoms and decreased quality of life. Currently available treatment options target symptoms but 25 do not address the underlying issue of joint tissue degeneration. As such, a better understanding of 26 the molecular mechanisms maintaining cartilage health is needed for developing novel therapeutic 27 strategies. Liver X Receptors (LXRs) are nuclear receptors that have been previously shown to 28 offer protection against OA. This is potentially due to suppression of chondrocyte hypertrophy in 29 endochondral bone growth in response to LXR activation. In order to better understand the 30 regulatory mechanisms behind this effect, we aimed to systematically examine LXR's effects on 31 growth plate chondrocyte gene expression. 32Methods: Primary chondrocytes isolated from the long bones of E15.5 mice were treated with the 33 specific LXR agonist, GW3965, and RNA was isolated for Affymetrix microarrays followed by 34 real time qPCR validation. Bioinformatics analyses were performed using Gene Ontology (GO) 35and KEGG pathway analysis. Immunohistochemistry was conducted to examine protein 36 localization of LXR and identified targets in GW3965-treated E15.5 tibiae compared to control. 37Results: Activation of LXR in primary growth plate chondrocytes resulted in differential 38 regulations of various genes involved in lipid metabolism, including several genes involved in 39 cholesterol efflux. This pattern was compared to LXR activation in immature murine articular 40 chondrocytes (IMACs), which revealed similar roles in lipid homeostasis. Immunohistochemical 41 analysis of LXR and its identified targets Abca1 and Srebf1 revealed preferential protein 42 localization to pre-hypertrophic and resting chondrocytes in GW3965-treated tibial growth plates 43 compared to controls. 44 Conclusion:Our findings show for the first time that LXR activation alters expression of lipid 45 metabolism genes in growth plate chondrocytes, in part through activation of molecules

show abstract

Sirt3 Promotes Chondrogenesis, Chondrocyte Mitochondrial Respiration and the Development of High-Fat Diet-Induced Osteoarthritis in Mice

Zhu

Donovan

Makosa

et al. 2020

Journal of Bone and Mineral Research

View full text Add to dashboard Cite

Understanding how obesity‐induced metabolic stress contributes to synovial joint tissue damage is difficult because of the complex role of metabolism in joint development, maintenance, and repair. Chondrocyte mitochondrial dysfunction is implicated in osteoarthritis (OA) pathology, which motivated us to study the mitochondrial deacetylase enzyme sirtuin 3 (Sirt3). We hypothesized that combining high‐fat‐diet (HFD)‐induced obesity and cartilage Sirt3 loss at a young age would impair chondrocyte mitochondrial function, leading to cellular stress and accelerated OA. Instead, we unexpectedly found that depleting cartilage Sirt3 at 5 weeks of age using Sirt3‐flox and Acan‐CreERT2 mice protected against the development of cartilage degeneration and synovial hyperplasia following 20 weeks of HFD. This protection was associated with increased cartilage glycolysis proteins and reduced mitochondrial fatty acid metabolism proteins. Seahorse‐based assays supported a mitochondrial‐to‐glycolytic shift in chondrocyte metabolism with Sirt3 deletion. Additional studies with primary murine juvenile chondrocytes under hypoxic and inflammatory conditions showed an increased expression of hypoxia‐inducible factor (HIF‐1) target genes with Sirt3 deletion. However, Sirt3 deletion impaired chondrogenesis using a murine bone marrow stem/stromal cell pellet model, suggesting a context‐dependent role of Sirt3 in cartilage homeostasis. Overall, our data indicate that Sirt3 coordinates HFD‐induced changes in mature chondrocyte metabolism that promote OA. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

show abstract

Nuclear receptors regulate lipid metabolism and oxidative stress markers in chondrocytes

Cited by 37 publications

References 53 publications

Guyanxiao formula antagonizes LPS-induced KOA chondrocyte injury by regulating the SDF-1 / CXCR4 signaling pathway1

Guyanxiao formula antagonizes LPS-induced KOA chondrocyte injury by regulating the SDF-1 / CXCR4 signaling pathway1

Liver X Receptor activation regulates genes involved in lipid homeostasis in developing chondrocytes

Sirt3 Promotes Chondrogenesis, Chondrocyte Mitochondrial Respiration and the Development of High-Fat Diet-Induced Osteoarthritis in Mice

Contact Info

Product

Resources

About