Taraxasterol inhibits inflammation in osteoarthritis rat model by regulating miRNAs and NF-κB signaling pathway.

Osteoarthritis (OA) has a high incidence rate in the elderly population and is a cause of chronic degenerative joint disease. Current therapeutic approaches to OA are effective but come with some side effects. Therefore, it is urgent to find new safe and effective OA treatments. This study aimed to clarify the function of taraxasterol (TAX) isolated from Taraxacum officinale in the papain-induced rat OA model. We observed that TAX alleviated the typical OA-caused phenomena in the joint. The expression of serum inflammatory mediators such as TNF-α, IL-6, and IL-1β was also repressed by TAX. In addition, NF-κB signaling pathway was repressed by TAX. Furthermore, two microRNAs: miR-140 and miR-146a were elevated after TAX treatment in OA rat model. Interestingly, several common targets of miR-140 and miR-146a, including HSPA4L, ST5, and ERBB4, were confirmed to be regulated by TAX. Inflammatory response related genes including S100A8, CCL3, A2M, LBP, and CCR1 were repressed by TAX in OA rat model. In summary, TAX inhibits inflammation in osteoarthritis rat model. Inflammatory mediators, NF-κB pathway and miR-140/miR-146a targets mediate the function of TAX.

[1]  Huilin Yang,et al.  Kartogenin prevents cartilage degradation and alleviates osteoarthritis progression in mice via the miR-146a/NRF2 axis , 2021, Cell Death & Disease.

[2]  Shan-Chi Liu,et al.  Targeting CCN Proteins in Rheumatoid Arthritis and Osteoarthritis , 2021, International journal of molecular sciences.

[3]  D. Ouyang,et al.  Inhibition of NLRP3 Inflammasome Activation and Pyroptosis in Macrophages by Taraxasterol Is Associated With Its Regulation on mTOR Signaling , 2021, Frontiers in Immunology.

[4]  Mina Wang,et al.  Mechanism of Traditional Chinese Medicine in Treating Knee Osteoarthritis , 2020, Journal of pain research.

[5]  A. Tsezou,et al.  The synergistic function of miR-140-5p and miR-146a on TLR4-mediated cytokine secretion in osteoarthritic chondrocytes. , 2019, Biochemical and biophysical research communications.

[6]  X. Weng,et al.  MIR-140-5p affects chondrocyte proliferation, apoptosis, and inflammation by targeting HMGB1 in osteoarthritis , 2019, Inflammation Research.

[7]  Xiao-Feng Zhu,et al.  Platelet-secreted CCL3 and its receptor CCR5 promote invasive and migratory abilities of anaplastic thyroid carcinoma cells via MMP-1. , 2019, Cellular signalling.

[8]  Yoonkyung Park,et al.  NF-κB Signaling Pathways in Osteoarthritic Cartilage Destruction , 2019, Cells.

[9]  Miaomiao Zhang,et al.  Taraxasterol suppresses inflammation in IL‐1&bgr;‐induced rheumatoid arthritis fibroblast‐like synoviocytes and rheumatoid arthritis progression in mice , 2019, International immunopharmacology.

[10]  Liqun Jiang,et al.  miR-140-5p/miR-149 Affects Chondrocyte Proliferation, Apoptosis, and Autophagy by Targeting FUT1 in Osteoarthritis , 2018, Inflammation.

[11]  Qian Chen,et al.  Evidence that miR‐146a attenuates aging‐ and trauma‐induced osteoarthritis by inhibiting Notch1, IL‐6, and IL‐1 mediated catabolism , 2018, Aging cell.

[12]  Dieter Rosenbaum,et al.  Objective assessment of physical activity and sedentary behaviour in knee osteoarthritis patients – beyond daily steps and total sedentary time , 2018, BMC Musculoskeletal Disorders.

[13]  C. Abraham,et al.  ErbB4 signaling stimulates pro-inflammatory macrophage apoptosis and limits colonic inflammation , 2017, Cell Death and Disease.

[14]  T. Hügle,et al.  What drives osteoarthritis?—synovial versus subchondral bone pathology , 2016, Rheumatology.

[15]  Wang Tiejun,et al.  Taraxasterol inhibits cigarette smoke-induced lung inflammation by inhibiting reactive oxygen species-induced TLR4 trafficking to lipid rafts. , 2016, European journal of pharmacology.

[16]  Jian Wang,et al.  Comparison of molecular mechanisms of rheumatoid arthritis and osteoarthritis using gene microarrays , 2016, Molecular medicine reports.

[17]  M. Nugent.  MicroRNAs: exploring new horizons in osteoarthritis. , 2016, Osteoarthritis and cartilage.

[18]  F. Lafeber,et al.  IL-1β, in contrast to TNFα, is pivotal in blood-induced cartilage damage and is a potential target for therapy. , 2015, Blood.

[19]  Zhe Zhang,et al.  The potent tumor suppressor miR-497 inhibits cancer phenotypes in nasopharyngeal carcinoma by targeting ANLN and HSPA4L , 2015, Oncotarget.

[20]  R. Chamy,et al.  Taraxacum officinale and related species-An ethnopharmacological review and its potential as a commercial medicinal plant. , 2015, Journal of ethnopharmacology.

[21]  Zhiqiang Ma,et al.  Taraxasterol inhibits IL-1β-induced inflammatory response in human osteoarthritic chondrocytes. , 2015, European journal of pharmacology.

[22]  Xuemei Zhang,et al.  Effects of taraxasterol on iNOS and COX-2 expression in LPS-induced RAW 264.7 macrophages. , 2014, Journal of ethnopharmacology.

[23]  C. Park,et al.  TOP 1 and 2, polysaccharides from Taraxacum officinale, inhibit NFκB-mediated inflammation and accelerate Nrf2-induced antioxidative potential through the modulation of PI3K-Akt signaling pathway in RAW 264.7 cells. , 2014, Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association.

[24]  Xuemei Zhang,et al.  Protective effect of taraxasterol against LPS-induced endotoxic shock by modulating inflammatory responses in mice , 2014, Immunopharmacology and immunotoxicology.

[25]  J. Pelletier,et al.  NFAT3 and TGF-β/SMAD3 regulate the expression of miR-140 in osteoarthritis , 2013, Arthritis Research & Therapy.

[26]  T. Deguchi,et al.  CCR1/CCL5 interaction promotes invasion of taxane-resistant PC3 prostate cancer cells by increasing secretion of MMPs 2/9 and by activating ERK and Rac signaling. , 2013, Cytokine.

[27]  C. Cooper,et al.  Epidemiology and burden of osteoarthritis. , 2013, British medical bulletin.

[28]  Xuemei Zhang,et al.  Effects of taraxasterol on inflammatory responses in lipopolysaccharide-induced RAW 264.7 macrophages. , 2012, Journal of ethnopharmacology.

[29]  James D. Kang,et al.  Human Nucleus Pulposus Cells React to IL-6: Independent Actions and Amplification of Response to IL-1 and TNF-&agr; , 2011, Spine.

[30]  Xuemei Zhang,et al.  Taraxacum officinale protects against lipopolysaccharide-induced acute lung injury in mice. , 2010, Journal of ethnopharmacology.

[31]  H. Youn,et al.  TOP1 and 2, polysaccharides from Taraxacum officinale, attenuate CCl(4)-induced hepatic damage through the modulation of NF-kappaB and its regulatory mediators. , 2010, Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association.

[32]  P. Eysel,et al.  The epidemiology, etiology, diagnosis, and treatment of osteoarthritis of the knee. , 2010, Deutsches Arzteblatt international.

[33]  A. Mobasheri,et al.  Synergistic chondroprotective effects of curcumin and resveratrol in human articular chondrocytes: inhibition of IL-1β-induced NF-κB-mediated inflammation and apoptosis , 2009, Arthritis research & therapy.

[34]  C. Lim,et al.  Anti-inflammatory activity of Taraxacum officinale. , 2008, Journal of ethnopharmacology.

[35]  Hui Li,et al.  Extracts from plastrum testudinis promote proliferation of rat bone‐marrow‐derived mesenchymal stem cells , 2007, Cell proliferation.

[36]  M. Kawaichi,et al.  Expression of mouse HtrA1 serine protease in normal bone and cartilage and its upregulation in joint cartilage damaged by experimental arthritis. , 2005, Bone.

[37]  E. Basch,et al.  Evidence-Based Systematic Review of Dandelion (Taraxacum officinale) by Natural Standard Research Collaboration , 2005, Journal of herbal pharmacotherapy.

[38]  J. Mort,et al.  Articular cartilage and changes in arthritis: Matrix degradation , 2001, Arthritis research.