scholarly journals Xanthohumol Inhibited Mechanical Stimulation-Induced Articular ECM Degradation by Mediating lncRNA GAS5/miR-27a Axis

2021 ◽  
Vol 12 ◽  
Author(s):  
Tiansheng Zheng ◽  
Qingluo Zhou ◽  
Jishang Huang ◽  
Jinliang Lai ◽  
Guanglin Ji ◽  
...  
Keyword(s):  
Mechanical Stimulation ◽  
Great Effort ◽  
Protective Effects ◽  
Joint Cartilage ◽  
Matrix Metalloproteinase 13 ◽  
Naturally Occurring ◽  
Potential Biomarker ◽  
Ecm Degradation ◽  
Oa Chondrocytes ◽  
Lncrna Gas5

Osteoarthritis (OA) is histopathologically marked by extracellular matrix (ECM) degradation in joint cartilage. Abnormal mechanical stimulation on joint cartilage may result in ECM degeneration and OA development. Matrix metalloproteinase 13 (MMP-13) is one of the catabolic enzymes contributing to the degradation of ECM, and it has become the potential biomarker for the therapeutic management of OA. Xanthohumol (XH), a naturally occurring prenylflavonoid derived from hops and beer, shows the protective activity against OA development. However, the potential mechanisms still need great effort. In this article, mechanical stimulation could significantly increase the expression of MMP-13 and lncRNA GAS5 (GAS5) and promoting ECM degradation. These could be effectively reversed by XH administration. Suppressed expression GAS5 ameliorated mechanical stimulation-induced MMP-13 expression. MiR-27a was predicted and verified as a target of GAS5, and overexpression of miR-27a down regulated the expression of MMP-13. Collectively, XH exhibited protective effects against mechanical stimulation-induced ECM degradation by mediating the GAS5/miR-27a signaling pathway in OA chondrocytes.

scholarly journals N6-Furfuryladenine is protective in Huntington’s disease models by signaling huntingtin phosphorylation

2018 ◽  
Vol 115 (30) ◽  
pp. E7081-E7090 ◽  
Author(s):  
Laura E. Bowie ◽  
Tamara Maiuri ◽  
Melanie Alpaugh ◽  
Michelle Gabriel ◽  
Nicolas Arbez ◽  
...  
Keyword(s):  
Dna Damage ◽  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Oxidative Dna Damage ◽  
Model Systems ◽  
Protective Effects ◽  
Mutant Huntingtin ◽  
Naturally Occurring ◽  
Phosphate Donor ◽  
High Content Analysis

The huntingtin N17 domain is a modulator of mutant huntingtin toxicity and is hypophosphorylated in Huntington’s disease (HD). We conducted high-content analysis to find compounds that could restore N17 phosphorylation. One lead compound from this screen was N6-furfuryladenine (N6FFA). N6FFA was protective in HD model neurons, and N6FFA treatment of an HD mouse model corrects HD phenotypes and eliminates cortical mutant huntingtin inclusions. We show that N6FFA restores N17 phosphorylation levels by being salvaged to a triphosphate form by adenine phosphoribosyltransferase (APRT) and used as a phosphate donor by casein kinase 2 (CK2). N6FFA is a naturally occurring product of oxidative DNA damage. Phosphorylated huntingtin functionally redistributes and colocalizes with CK2, APRT, and N6FFA DNA adducts at sites of induced DNA damage. We present a model in which this natural product compound is salvaged to provide a triphosphate substrate to signal huntingtin phosphorylation via CK2 during low-ATP stress under conditions of DNA damage, with protective effects in HD model systems.

scholarly journals TGF-β type 2 receptor–mediated modulation of the IL-36 family can be therapeutically targeted in osteoarthritis

2019 ◽  
Vol 11 (491) ◽  
pp. eaan2585 ◽  
Author(s):  
Tieshi Li ◽  
Susan Chubinskaya ◽  
Alessandra Esposito ◽  
Xin Jin ◽  
Lidia Tagliafierro ◽  
...  
Keyword(s):  
Receptor Antagonist ◽  
Therapeutic Agent ◽  
Human Tissues ◽  
Human Cartilage ◽  
Joint Development ◽  
Naturally Occurring ◽  
Oa Chondrocytes ◽  
Disease Modifying ◽  
Surgical Conditions

Mechanisms that govern the shift from joint homeostasis to osteoarthritis (OA) remain unknown. Here, we identify a pathway used for joint development and homeostasis, and its role in OA. Using a combination of transgenic, pharmacological, and surgical conditions in mouse and human tissues, we found that TGF-β signaling promotes joint homeostasis through regulation of the IL-36 family. We identified IL-36 receptor antagonist (IL-36 in mice and IL-36RN in humans) as a potential disease-modifying OA drug. Specifically, OA development was associated with IL-36α up-regulation and IL-36Ra down-regulation in mice with tissue-specific postnatally induced ablation of Tgfbr2, mice treated with a TGF-β signaling inhibitor, mice with posttraumatic OA, and aging mice with naturally occurring OA. In human cartilage, OA severity was associated with decreased TGFBR2 and IL-36RN, whereas IL-36α increased. Functionally, intra-articular treatment with IL-36Ra attenuated OA development in mice, and IL-36RN reduced MMP13 in human OA chondrocytes. These findings highlight the relevance of TGFBR2–IL-36 interplay in joint homeostasis and IL-36RN as a potential therapeutic agent for OA.

Pluripotent Protective Effects of Carnosine, a Naturally Occurring Dipeptidea

1998 ◽  
Vol 854 (1 TOWARDS PROLO) ◽  
pp. 37-53 ◽  
Author(s):  
A. R. HIPKISS ◽  
J. E. PRESTON ◽  
D.T. M. HIMSWORTH ◽  
V. C. WORTHINGTON ◽  
M. KEOWN ◽  
...  
Keyword(s):  
Protective Effects ◽  
Naturally Occurring

scholarly journals Simvastatin Inhibits CYR61 Expression in Orbital Fibroblasts in Graves’ Ophthalmopathy through the Regulation of FoxO3a Signaling

2021 ◽  
Vol 2021 ◽  
pp. 1-12
Author(s):  
Yi-Hsuan Wei ◽  
Shu-Lang Liao ◽  
Chia-Chun Wang ◽  
Sen-Hsu Wang ◽  
Wan-Chun Tang ◽  
...  
Keyword(s):  
Inflammatory Diseases ◽  
Protective Effects ◽  
Cellular Mechanisms ◽  
Graves Ophthalmopathy ◽  
Potential Biomarker ◽  
Tnf Α ◽  
Orbital Tissue ◽  
Proinflammatory Role ◽  
And Migration ◽  
Orbital Fibroblasts

Graves’ ophthalmopathy (GO), which is characterized by orbital tissue inflammation, expansion, and fibrosis, is the ocular manifestation in 25% to 50% of patients with Graves’ disease. As the pathology of GO is driven by autoimmune inflammation, many proinflammatory cytokines/chemokines, including TNF-α, IL-1β, IL-6, and CCL20, are crucial in the pathogenesis of GO to activate the orbital fibroblasts. Cysteine-rich protein 61 (CYR61), which is known to regulate cell proliferation, adhesion, and migration, plays a proinflammatory role in the pathogenesis of many inflammatory diseases, such as rheumatoid arthritis. CYR61 was considered a potential biomarker of GO in recent studies. Statins, which are cholesterol-lowering drugs, were found to reduce the risk of GO, probably through their anti-inflammatory and immunomodulatory effects. In this study, we established a link between CYR61 and statins in the pathogenesis and potential treatment for GO. Firstly, our data showed the overexpression of CYR61 in the orbital tissue ( n = 4 ) and serum specimens ( n = 6 ) obtained from the patients with inactive GO. CYR61 could induce the production of IL-6 and CCL20 in cultured GO orbital fibroblasts. The expression of CYR61 in cultured GO orbital fibroblasts was upregulated via TNF-α stimulation. Secondly, we pretreated cultured GO orbital fibroblasts using simvastatin, a statin, followed by TNF-α stimulation. The data revealed that simvastatin could inhibit TNF-α-induced CYR61 expression by modulating the activity of transcription factor FoxO3a. Our results provided insights into some cellular mechanisms that may explain the possible protective effects of simvastatin against the development of GO.

scholarly journals Mangiferin Prevents TBHP-Induced Apoptosis and ECM Degradation in Mouse Osteoarthritic Chondrocytes via Restoring Autophagy and Ameliorates Murine Osteoarthritis

2019 ◽  
Vol 2019 ◽  
pp. 1-17 ◽  
Author(s):  
Yao Li ◽  
Yaosen Wu ◽  
Kaixia Jiang ◽  
Wen Han ◽  
Jing Zhang ◽  
...  
Keyword(s):  
Protective Effect ◽  
Chondrocyte Apoptosis ◽  
Protective Effects ◽  
Ampk Signaling ◽  
Age Related ◽  
Osteoarthritic Chondrocytes ◽  
Ecm Degradation ◽  
Induced Apoptosis ◽  
Amp Activated Protein Kinase

Osteoarthritis (OA) is an age-related degenerative disease with complicated pathology involving chondrocyte apoptosis and extracellular matrix (ECM) degradation. Previous studies have shown that moderate autophagy has a protective effect against apoptosis in chondrocyte. Mangiferin is a natural polyphenol and exerts multiple pharmacological effects on different diseases in various preclinical studies. In this study, we investigated the effects of mangiferin on OA and delineated a potential molecular mechanism. In vitro, mangiferin treatment inhibited the expression of proapoptotic proteins induced by tert-butyl hydroperoxide (TBHP), increased the expression of antiapoptotic Bcl-2, and prevented ECM degradation by inhibiting the production of matrix-degrading enzyme. Mechanistically, mangiferin enhanced autophagy by activating the AMP-activated protein kinase (AMPK) signaling pathway. On the contrary, inhibition of autophagy partly abolished the protective effects of mangiferin on antiapoptosis and ECM synthesis in TBHP-treated chondrocyte. Correspondingly, the protective effect of mangiferin was also found in a mouse OA model. In conclusion, our results suggested that mangiferin serves as a potentially applicable candidate for treating OA.

Haem oxygenase-1: a target for dietary antioxidants

2004 ◽  
Vol 32 (6) ◽  
pp. 1003-1005 ◽  
Author(s):  
R.M. Ogborne ◽  
S.A. Rushworth ◽  
C.A. Charalambos ◽  
M.A. O'Connell
Keyword(s):  
Stress Response ◽  
Animal Models ◽  
Vascular Disease ◽  
Cell Types ◽  
Protective Role ◽  
Dietary Therapy ◽  
Protective Effects ◽  
Dietary Antioxidants ◽  
Naturally Occurring ◽  
Haem Oxygenase

HO-1 (haem oxygenase-1) is a stress-response enzyme involved in the catabolism of haem. In animal models, it plays a key protective role in vascular disease. HO-1 has anti-inflammatory effects in macrophages and is induced by a range of stimuli, including antioxidants, in various cell types. As dietary antioxidants are considered to be beneficial in vascular disease, their protective effects may occur through induction of HO-1. Emerging evidence suggests that a range of dietary and other naturally occurring antioxidants stimulate HO-1 expression in various cell types, although regulation by these compounds has not been investigated in detail. These studies suggest that HO-1 may be a target for dietary therapy in vascular disease.

Sign in / Sign up

Export Citation Format

Share Document