Pravastatin ameliorated osteoarthritis susceptibility in male offspring rats induced by prenatal ethanol exposure

Ni, Qubo; Chen, Haitao; Wei, Li; Lu, Kaihang; Li, Bin; Tan, Yang; Wang, Hui; Chen, Liaobin

doi:10.1016/j.bone.2021.115976

Cited by 8 publications

(4 citation statements)

References 39 publications

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“…Statins have dihydroxyheptanoic acid structure, either lactone ring or open ring hydroxyl acid, but lactone ring types must be transformed into corresponding open ring hydroxyl acid form in vivo to play pharmacological effects, so pravastatin having direct pharmacological activity was used in this study. Pravastatin could protect osteoarthritis chondrocytes by inhibiting autophagy and reducing inflammation and matrix degradation [ 17 , 18 ]. The results showed that pravastatin could significantly reduce the expression of matrix metalloproteinases MMP-1 and MMP-13 in IL-1 β -mediated human OA model chondrocytes, which was consistent with the results of relevant studies.…”

Section: Discussionmentioning

confidence: 99%

Pravastatin Reduces Matrix Metalloproteinases Expression and Promotes Cholesterol Efflux in Osteoarthritis Chondrocytes

Guo

et al. 2022

Evidence-Based Complementary and Alternative Medicine

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Background. Chondrocyte metabolic disorder plays an important role in the development of osteoarthritis (OA). The use of statins in the treatment of OA has also been widely studied, but the mechanism is still confusing. The present study aims to investigate the effects of statin on osteoarthritis chondrocytes and its underlying mechanism. Major findings. An untargeted metabolomics study revealed that the treatment of statins significantly changed the metabolites of articular cartilage tissues collected from female osteoarthritis patients, and might be involved in the glycerophospholipid metabolism pathway. In vitro study showed that 5–50 μmol/L of pravastatin exerts no cytotoxicity on human chondrocytes. Besides, 50 μmol/L of pravastatin caused a significant decrease in the expression of matrix metalloproteinase (MMP)-1 and MPP-13, and intracellular cholesterol in interleukin-1β (IL-1β)-induced human chondrocytes. Furthermore, at both mRNA and protein levels, the expression of the proteins related to the cholesterol efflux pathway (liver X receptor and cholesterol efflux regulatory protein) were significantly up-regulated by 50 μmol/L of pravastatin in IL-1β-induced human chondrocytes. Conclusion. Pravastatin can reduce the expression of MMPs in IL-1β-induced human chondrocytes and protect the chondrocyte matrix. The mechanism may be related to promoting the expression of proteins related to the cholesterol efflux pathway and reducing the level of cellular cholesterol.

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Section: Discussionmentioning

confidence: 99%

Pravastatin Reduces Matrix Metalloproteinases Expression and Promotes Cholesterol Efflux in Osteoarthritis Chondrocytes

Guo

et al. 2022

Evidence-Based Complementary and Alternative Medicine

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“…Caspase-8 is widely accepted as an apical apoptotic factor involved in cell death pathways including intrinsic and extrinsic apoptosis that is critically vital for the progression of OA [ 41 ]. Ni et al discovered that Pravastatin significantly reduced high expression of Caspase-8 in articular cartilage in order to reverse apoptosis of chondrocytes in OA rats [ 42 ].…”

Section: Discussionmentioning

confidence: 99%

A Study on the Potential Mechanism of Shujin Dingtong Recipe against Osteoarthritis Based on Network Pharmacology and Molecular Docking

Yuan

Yang

2022

Computational and Mathematical Methods in Medicine

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Background. With the aging of the social population, Osteoarthritis (OA) has already become a vital health and economic problem globally. Shujin Dingtong recipe (SJDTR) is an effective formula to treat OA in China. Although studies have shown that SJDTR can significantly alleviate OA symptoms, its mechanism still remains unclear. Purpose. This study is aimed at investigating the potential mechanism of SJDTR for the treatment of OA based on network pharmacology and molecular docking. Methods. Main ingredients of SJDTR were retrieved from the Traditional Chinese Medicine Systems Pharmacology (TCMSP) database. OA disease targets were obtained from the Gene Expression Omnibus (GEO) database. The overlapped targets and signaling pathways were explored using Protein-Protein Interaction (PPI) network, Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG). Following this, the core targets were employed to dock with corresponding components via molecular docking in order to further explore the mechanism of SJDTR in the treatment of OA. Results. From network pharmacology, we found 100 active components of SJDTR, 31 drug and OA-related targets, 1161 GO items, and 91 signaling pathways. Based on the analysis with PPI network and molecular docking, TP53, CCNB1, and MMP-2 were selected for the core targets of SJDTR against OA. Molecular docking demonstrated that Quercetin, Baicalein, and Luteolin, had good binding with the TP53, CCNB1, and MMP-2 protein, respectively. Conclusion. To conclude, our study suggested the main ingredients of SJDTR might alleviate the progression of OA through multiple targets and pathways. Additionally, network pharmacology and molecular docking, as new approaches, were adopted for systematically exploring the potential mechanism of SJDTR for the treatment of OA.

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“…Therefore, it can be concluded that pravastatin significantly reduces inflammation and matrix breakdown and improves OA susceptibilities in articular cartilage, reducing the buildup of cholesterol throughout chondrocytes. 100,101 Figure 1 shows signaling pathways for pravastatin in cartilage degradation.…”

Section: Effect Of Pravastatin On Oamentioning

confidence: 99%

Therapeutic effects of statins on osteoarthritis: A review

Saberianpour

Abolbashari

Modaghegh

et al. 2022

J of Cellular Biochemistry

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Osteoarthritis (OA) is a progressive joint disease. The etiology of OA is considered to be multifactorial. Currently, there is no definitive treatment for OA, and the existing treatments are not very effective. Hypercholesterolemia is considered a novel risk factor for the development of OA. Statins act as a competitive inhibitor of the β‐hydroxy β‐methylglutaryl‐CoA (HMG‐CoA) reductase and are widely used to manage hypercholesterolemia. Inhibition of HMG‐CoA reductase results in reduced synthesis of a metabolite named mevalonate, thereby reducing cholesterol biosynthesis in subsequent steps. By this mechanism, statins such as atorvastatin and simvastatin could potentially have a preventive impact on joint cartilage experiencing osteoarthritic deterioration by reducing serum cholesterol levels. Atorvastatin can protect cartilage degradation following interleukin‐1β‐stimulation. Atorvastatin stimulates the STAT1‐caspase‐3 signaling pathway that was shown to be responsible for its anti‐inflammatory effects on the knee joint. Simvastatin had chondroprotective effects on OA in vitro by reducing matrix metalloproteinases expression patterns. In this study, we tried to review the therapeutic effects of statins on OA.

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Pravastatin ameliorated osteoarthritis susceptibility in male offspring rats induced by prenatal ethanol exposure

Cited by 8 publications

References 39 publications

Pravastatin Reduces Matrix Metalloproteinases Expression and Promotes Cholesterol Efflux in Osteoarthritis Chondrocytes

Pravastatin Reduces Matrix Metalloproteinases Expression and Promotes Cholesterol Efflux in Osteoarthritis Chondrocytes

A Study on the Potential Mechanism of Shujin Dingtong Recipe against Osteoarthritis Based on Network Pharmacology and Molecular Docking

Therapeutic effects of statins on osteoarthritis: A review

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