Correlation network analysis shows divergent effects of a long-term, high-fat diet and exercise on early stage osteoarthritis phenotypes in mice

Griffin, Timothy M.; Batushansky, Albert; Hudson, Joanna Q.; Lopes, Erika Barboza Prado

doi:10.1016/j.jshs.2019.05.008

Cited by 18 publications

(11 citation statements)

References 52 publications

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“…Correlation network analysis takes advantage of within-group variation to integrate data across different levels of biological organization and function and identify relationships among multiple groups of variables [70].…”

Section: Effect Of Gut Microbiota Dysbiosis On Oa Network Correlationmentioning

confidence: 99%

Gut microbiome dysbiosis alleviates the progression of osteoarthritis in mice

et al. 2020

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Gut microbiota dysbiosis has been studied under the pathological conditions of osteoarthritis (OA). However, the effect of antibiotic-induced gut flora dysbiosis on OA remains incompletely understood at present. Herein, we used a mouse (8 weeks) OA model of destabilization of the medial meniscus (DMM) and gut microbiome dysbiosis induced by antibiotic treatment with ampicillin and neomycin for 8 weeks. The results show that antibiotic-induced intestinal microbiota dysbiosis reduced the serum level of lipopolysaccharide (LPS) and the inflammatory response, such as suppression of the levels of tumour necrosis factor-α (TNF-α) and interleukin-6 (IL-6), which can lead to decreased matrix metalloprotease-13 (MMP-13) expression and improvement of OA after joint injury. In addition, trabecular thickness (Tb.Th) and osteophyte scores were increased significantly in antibiotic-induced male mice compared with female mice. We further used network correlation analysis to verify the effect of gut microbiota dysbiosis on OA. Therefore, this study contributes to our understanding of the gut-joint axis in OA and reveals the relationship between the inflammatory response, sex and gut microbiota, which may provide new strategies to prevent the symptoms and long-term sequelae of OA.

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Section: Effect Of Gut Microbiota Dysbiosis On Oa Network Correlationmentioning

confidence: 99%

Gut microbiome dysbiosis alleviates the progression of osteoarthritis in mice

et al. 2020

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“…Isolated knee joints were fixed and embedded in paraffin as previously described, excluding micro-computed tomography analysis. 21 Sections from 22- and 56-week-old mice that underwent DMM surgery were used for SIRT5 immunostaining. Isolated knee joints were fixed in freshly prepared 4% paraformaldehyde for 48 hours at 3 °C, decalcified in Cal-Ex Decalcifier (Fisher Chemical) for 3 days at 3 °C, dehydrated, and embedded in paraffin for coronal sectioning.…”

Section: Methodsmentioning

confidence: 99%

Sirt5 Deficiency Causes Posttranslational Protein Malonylation and Dysregulated Cellular Metabolism in Chondrocytes Under Obesity Conditions

et al. 2021

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Objective Obesity accelerates the development of osteoarthritis (OA) during aging and is associated with altered chondrocyte cellular metabolism. Protein lysine malonylation (MaK) is a posttranslational modification (PTM) that has been shown to play an important role during aging and obesity. The objective of this study was to investigate the role of sirtuin 5 (Sirt5) in regulating MaK and cellular metabolism in chondrocytes under obesity-related conditions. Methods MaK and SIRT5 were immunostained in knee articular cartilage of obese db/db mice and different aged C57BL6 mice with or without destabilization of the medial meniscus surgery to induce OA. Primary chondrocytes were isolated from 7-day-old WT and Sirt5−/− mice and treated with varying concentrations of glucose and insulin to mimic obesity. Sirt5-dependent effects on MaK and metabolism were evaluated by western blot, Seahorse Respirometry, and gas/chromatography-mass/spectrometry (GC-MS) metabolic profiling. Results MaK was significantly increased in cartilage of db/db mice and in chondrocytes treated with high concentrations of glucose and insulin (GluhiInshi). Sirt5 was increased in an age-dependent manner following joint injury, and Sirt5 deficient primary chondrocytes had increased MaK, decreased glycolysis rate, and reduced basal mitochondrial respiration. GC-MS identified 41 metabolites. Sirt5 deficiency altered 13 distinct metabolites under basal conditions and 18 metabolites under GluhiInshi treatment. Pathway analysis identified a wide range of Sirt5-dependent altered metabolic pathways that include amino acid metabolism, TCA cycle, and glycolysis. Conclusion This study provides the first evidence that Sirt5 broadly regulates chondrocyte metabolism. We observed changes in SIRT5 and MaK levels in cartilage with obesity and joint injury, suggesting that the Sirt5-MaK pathway may contribute to altered chondrocyte metabolism that occurs during OA development.

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“…Articular chondrocytes isolated from obese OA patients exhibit an altered response pattern to elevated leptin levels compared with lean or overweight patients [ 50 ]. Furthermore, a high-fat diet caused a robust increase in leptin that was positively correlated with OA-related cartilage damage, osteophytes, increased infrapatellar fat pad (IPFP) size, and elevated serum OA biomarkers (i.e., tissue inhibitor of metalloproteinases-1, and insulin-like growth factor-I) in obese mice [ 51 ]. A recent study by Sachdeva et al.…”

Section: The Challenges Of Articular Cartilage Regeneration In Obesitmentioning

confidence: 99%

Cartilage tissue engineering for obesity-induced osteoarthritis: Physiology, challenges, and future prospects

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Udduttula

et al. 2021

Journal of Orthopaedic Translation

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Correlation network analysis shows divergent effects of a long-term, high-fat diet and exercise on early stage osteoarthritis phenotypes in mice

Cited by 18 publications

References 52 publications

Gut microbiome dysbiosis alleviates the progression of osteoarthritis in mice

Gut microbiome dysbiosis alleviates the progression of osteoarthritis in mice

Sirt5 Deficiency Causes Posttranslational Protein Malonylation and Dysregulated Cellular Metabolism in Chondrocytes Under Obesity Conditions

Cartilage tissue engineering for obesity-induced osteoarthritis: Physiology, challenges, and future prospects

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