scholarly journals Obtusifolin, an Anthraquinone Extracted from Senna obtusifolia (L.) H.S.Irwin & Barneby, Reduces Inflammation in a Mouse Osteoarthritis Model

2021 ◽  
Vol 14 (3) ◽  
pp. 249
Author(s):  
Jiho Nam ◽  
Dong-Won Seol ◽  
Choong-Gu Lee ◽  
Gabbine Wee ◽  
Siyoung Yang ◽  
...  
Keyword(s):  
Cartilage Damage ◽  
Cartilage Destruction ◽  
Collagenase Activity ◽  
Senna Obtusifolia ◽  
Pge2 Level ◽  
Age Related ◽  
Safranin O ◽  
Cox2 Expression

Osteoarthritis (OA) is an age-related degenerative disease that causes cartilage dysfunction and inflammation. Obtusifolin, an anthraquinone extracted from Senna obtusifolia (L.) H.S.Irwin & Barneby seeds, has anti-inflammatory functions; it could be used as a drug component to relieve OA symptoms. In this study, we investigated the effects of obtusifolin on OA inflammation. In vitro, interleukin (IL)-1β (1 ng/mL)-treated mouse chondrocytes were co-treated with obtusifolin at different concentrations. The expression of matrix metalloproteinase (Mmp) 3, Mmp13, cyclooxygenase 2 (Cox2), and signaling proteins was measured by polymerase chain reaction and Western blotting; collagenase activity and the PGE2 level were also determined. In vivo, OA-induced C57BL/6 mice were administered obtusifolin, and their cartilage was stained with Safranin O to observe damage. Obtusifolin inhibited Mmp3, Mmp13, and Cox2 expression to levels similar to or more than those after treatment with celecoxib. Additionally, obtusifolin decreased collagenase activity and the PGE2 level. Furthermore, obtusifolin regulated OA via the NF-κB signaling pathway. In surgically induced OA mouse models, the cartilage destruction decreased when obtusifolin was administered orally. Taken together, our results show that obtusifolin effectively reduces cartilage damage via the regulation of MMPs and Cox2 expression. Hence, we suggest that obtusifolin could be a component of another OA symptom reliever.

scholarly journals Human Umbilical Mesenchymal Stromal Cells Mixed with Hyaluronan Transplantation Decreased Cartilage Destruction in a Rabbit Osteoarthritis Model

2021 ◽  
Vol 2021 ◽  
pp. 1-12
Author(s):  
Yu-Hsun Chang ◽  
Dah-Ching Ding ◽  
Kun-Chi Wu
Keyword(s):  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Rabbit Model ◽  
Human Leukocyte ◽  
Type Ii Collagen ◽  
Cartilage Destruction ◽  
Human Umbilical Cord ◽  
Safranin O

Osteoarthritis (OA), the most common type of arthritis, causes pain in joints and disability. Due to the absence of ideal effective medication, stem cell transplantation emerges as a new hope for OA therapy. This study is aimed at evaluating the capability of human umbilical cord mesenchymal stromal cells (HUCMSCs) mixed with hyaluronan (HA) to treat osteoarthritis in a rabbit model. Differentiation capability of HUCMSCs, magnetic resonance image examination, and immunohistochemistry of the cartilage after transplantation of HUCMSCs mixed with HA in a rabbit OA model were explored. HUCMSCs exhibited typical mesenchymal stromal cell (MSC) characteristics, including spindle-shaped morphology, surface marker expressions (positive for human leukocyte antigen- (HLA-) ABC, CD44, CD73, CD90, and CD105; negative for HLA-DR, CD34, and CD45), and trilineage differentiation (chondrogenesis, adipogenesis, and osteogenesis). The gene expression of SOX9, type II collagen, and aggrecan in the HUCMSC-derived chondrocytes mixed with HA was increased after in vitro chondrogenesis compared with HUCMSCs. A gross and histological significant improvement in hyaline cartilage destruction after HUCMSCs mixed with HA was noted in the animal model compared to the OA knees. The International Cartilage Repair Society histological score and Safranin O staining were significantly higher for the treated knees than the control knees ( p < 0.05 ). Moreover, the expression of MMP13 was significantly decreased in the treated knees than in the OA knees. In conclusion, HUCMSCs mixed with HA in vitro and in vivo might attenuate the cartilage destruction in osteoarthritis. Our study provided evidence for future clinical trials.

scholarly journals Schisandrol A Suppresses Catabolic Factor Expression by Blocking NF-κB Signaling in Osteoarthritis

2021 ◽  
Vol 14 (3) ◽  
pp. 241
Author(s):  
Seong Jae Han ◽  
Jimoon Jun ◽  
Seong-il Eyun ◽  
Choong-Gu Lee ◽  
Jimin Jeon ◽  
...  
Keyword(s):  
Therapeutic Agent ◽  
Cartilage Destruction ◽  
Dependent Manner ◽  
Oral Gavage ◽  
Osteoarthritic Cartilage ◽  
Surgical Model ◽  
Dose Dependent ◽  
Cox2 Expression

Schisandrol A possesses pharmacological properties and is used to treat various diseases; however, its effects on osteoarthritis (OA) progression remain unclear. Here, we investigated Schisandrol A as a potential therapeutic agent for OA. In vitro, Schisandrol A effects were confirmed based on the levels of expression of catabolic factors (MMPs, ADAMTS5, and Cox2) induced by IL-1β or Schisandrol A treatment in chondrocytes. In vivo, experimental OA in mice was induced using a destabilized medial meniscus (DMM) surgical model or oral gavage of Schisandrol A in a dose-dependent manner, and demonstrated using histological analysis. In vitro and in vivo analyses demonstrated that Schisandrol A inhibition attenuated osteoarthritic cartilage destruction via the regulation of Mmp3, Mmp13, Adamts5, and Cox2 expression. In the NF-κB signaling pathway, Schisandrol A suppressed the degradation of IκB and the phosphorylation of p65 induced by IL-1β. Overall, and Schisandrol A reduced the expression of catabolic factors by blocking NF-κB signaling and prevented cartilage destruction. Therefore, Schisandrol A attenuated OA progression, and can be used to develop novel OA drug therapies.

scholarly journals LncRNA CRNED Hinders The Progression of Osteoarthritis By Epigenetic Regulation of DACT1

2021 ◽  
Author(s):  
Ziqi Zhang ◽  
Pei Yang ◽  
Chunsheng Wang ◽  
Run Tian
Keyword(s):  
Rat Model ◽  
Epigenetic Modification ◽  
Colorectal Neoplasia ◽  
Cruciate Ligament ◽  
Cartilage Damage ◽  
Cartilage Degeneration ◽  
Downstream Target ◽  
Age Related

Abstract Osteoarthritis (OA) is mainly characterized by articular cartilage degeneration, synovial fibrosis, and inflammation. LncRNA CRNED (colorectal neoplasia differentially expressed) has been reported to be down-regulated in age-related OA, but its role in injury-induced OA needs to be further explored. In this study, an OA rat model was established by using anterior cruciate ligament transection, and the adenovirus-mediated CRNED overexpression (Ad-CRNED) or DACT1 (dapper antagonist of catenin-1) interference (sh-DACT1) vectors were injected into the rat model via tail vein. Besides, chondrocyte‑like ATDC5 cells were treated with IL-1β (10 ng/mL) to simulate OA conditions in vitro. We found that overexpression of CRNED alleviated cartilage damage and synovitis in OA rats, and suppressed IL-1β-induced apoptosis, inflammation, and extracellular matrix (ECM) degradation in chondrocyte‑like ATDC5 cells, while silencing DACT1 effectively antagonized the protective effect of CRNED both in vivo and in vitro. Mechanism studies revealed that DACT1 could act as a downstream target of CRNED. By recruiting p300, CRNED promoted the enrichment of H3K27ac in the DACT1 promoter, thus promoting DACT1 transcription. In addition, CRNED hindered the activation of the Wnt/β-catenin pathway in IL-1β-stimulated cells by inducing DACT1 expression. In conclusion, CRNED promoted DACT1 expression through epigenetic modification and restrained the activation of Wnt/β-catenin signaling to impede the progression of OA.

scholarly journals Susceptibility of cyclin-dependent kinase inhibitor 1-deficient mice to rheumatoid arthritis arising from interleukin-1β-induced inflammation

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Yoshinori Takashima ◽  
Shinya Hayashi ◽  
Koji Fukuda ◽  
Toshihisa Maeda ◽  
Masanori Tsubosaka ◽  
...  
Keyword(s):  
Kinase Inhibitor ◽  
Cartilage Destruction ◽  
Cyclin Dependent Kinase ◽  
In Vivo Models ◽  
Cyclin Dependent Kinase Inhibitor ◽  
Tnf Α ◽  
Safranin O ◽  
And Cartilage

AbstractWe recently reported that cyclin-dependent kinase inhibitor 1 (p21) deficiency induces osteoarthritis susceptibility. Here, we determined the mechanism underlying the effect of p21 in synovial and cartilage tissues in RA. The knee joints of p21-knockout (p21−/−) (n = 16) and wild type C57BL/6 (p21+/+) mice (n = 16) served as in vivo models of collagen antibody-induced arthritis (CAIA). Arthritis severity was evaluated by immunological and histological analyses. The response of p21 small-interfering RNA (siRNA)-treated human RA FLSs (n = 5 per group) to interleukin (IL)-1β stimulation was determined in vitro. Arthritis scores were higher in p21−/− mice than in p21+/+ mice. More severe synovitis, earlier loss of Safranin-O staining, and cartilage destruction were observed in p21−/− mice compared to p21+/+ mice. p21−/− mice expressed higher levels of IL-1β, TNF-α, F4/80, CD86, p-IKKα/β, and matrix metalloproteinases (MMPs) in cartilage and synovial tissues via IL-1β-induced NF-kB signaling. IL-1β stimulation significantly increased IL-6, IL-8, and MMP expression, and enhanced IKKα/β and IκBα phosphorylation in human FLSs. p21-deficient CAIA mice are susceptible to RA phenotype alterations, including joint cartilage destruction and severe synovitis. Therefore, p21 may have a regulatory role in inflammatory cytokine production including IL-1β, IL-6, and TNF-α.

scholarly journals Platelet-rich plasma inhibits Adriamycin-induced inflammation via blocking the NF-κB pathway in articular chondrocytes

2021 ◽  
Vol 27 (1) ◽  
Author(s):  
Haijun Zhao ◽  
Weijie Zhu ◽  
Wude Mao ◽  
Chengkai Shen
Keyword(s):  
Articular Chondrocytes ◽  
Platelet Rich Plasma ◽  
Cartilage Destruction ◽  
Chondrocyte Apoptosis ◽  
Related Factors ◽  
Protein Levels ◽  
Cell Matrix ◽  
Safranin O

Abstract Background Previous studies showed that doxorubicin could lead to osteoarthritis (OA) by inducing chondrocyte inflammation and apoptosis. Besides, it is reported that platelet-rich plasma (PRP) could suppress the activation of inflammatory NF-κB signaling. Here, we aimed to determine whether PRP was able to exert a protective effect against doxorubicin-induced chondrocyte damages. Methods To determine whether PRP protects chondrocytes against destabilization of the medial meniscus (DMM)-induced osteoarthritis, mice were treated with PRP and doxorubicin, and the cartilage destruction was observed through Safranin O-fast green staining and osteoarthritis scoring. ELISA assay was used to check the release of TNF-α and ILs. In vitro, we treated chondrocytes with doxorubicin and PRP; CCK-8 was used to measure cell viability. Western blot, real-time PCR, and ELISA were applied to check apoptosis-related signaling and inflammation-associated factors. Results The results from the mouse model suggested that PRP attenuated doxorubicin-induced cartilage destruction in vivo. Doxorubicin promoted chondrocyte apoptosis while PRP ameliorated this damage. PRP inhibited doxorubicin-induced dysregulation of cell matrix-related factors, including SOX9, Col2A1, Col10A1, and Aggrecan, reduced protein levels of doxorubicin-induced inflammatory markers, COX-2, and iNOS, and blocked doxorubicin-induced phosphorylation of IκB and NF-κB in articular chondrocytes. Conclusions PRP improved doxorubicin-induced damage on chondrocytes. This research might provide a new theoretical basis for the clinical treatment of osteoarthritis caused by doxorubicin.

scholarly journals LncRNA CRNED Hinders the Progression of Osteoarthritis by Epigenetic Regulation of DACT1

2021 ◽  
Author(s):  
Ziqi Zhang ◽  
Pei Yang ◽  
Chunsheng Wang ◽  
Run Tian
Keyword(s):  
Rat Model ◽  
Epigenetic Modification ◽  
Colorectal Neoplasia ◽  
Cruciate Ligament ◽  
Cartilage Damage ◽  
Loss Of Function ◽  
Cell Functions ◽  
Age Related

Abstract Background: Osteoarthritis (OA) is usually characterized by articular cartilage degeneration, synovial fibrosis and inflammation. LncRNA CRNED (colorectal neoplasia differentially expressed) has been reported to be down-regulated in age-related OA, but its role in injury-induced OA needs to be further explored.Methods: An OA rat model was established by using anterior cruciate ligament transection, and the adenovirus-mediated CRNED overexpression (Ad-CRNED) or DACT1 (dapper antagonist of catenin-1) interference (sh-DACT1) vectors were injected into the rat model through tail vein. ATDC5 cells were treated by IL-1β (10 ng/mL) to simulate OA conditions in vitro. Histological staining was performed to evaluate knee cartilage damage and synovitis. Gain-and loss-of-function assays analyzed the effects of CRNED and DACT1 on cell functions and Wnt/β-catenin pathway activity in chondrocytes. Bioinformatic analysis, RNA immunoprecipitation and chromatin immunoprecipitation were used to assess the regulatory interaction of CRNED, p300 and DACT1.Results: Overexpression of CRNED alleviated cartilage damage and synovitis in OA rats, and suppressed IL-1β-induced apoptosis, inflammation, and extracellular matrix (ECM) degradation in DACT5 cells, while silencing DACT1 effectively antagonized the protective effect of CRNED both in vitro and in vivo. Mechanism studies found that DACT1 could act as a downstream target of CRNED. By recruiting p300, CRNED promoted the enrichment of H3K27ac in the DACT1 promoter, thus promoting DACT1 transcription. In addition, CRNED hindered the activation of the Wnt pathway in IL-1β-stimulated chondrocytes by inducing DACT1 expression.Conclusion: CRNED promoted DACT1 expression through epigenetic modification and restrained the activation of Wnt/β-catenin signaling to impede the progression of OA.

scholarly journals Regorafenib-Attenuated, Bleomycin-Induced Pulmonary Fibrosis by Inhibiting the TGF-β1 Signaling Pathway

2021 ◽  
Vol 22 (4) ◽  
pp. 1985
Author(s):  
Xiaohe Li ◽  
Ling Ma ◽  
Kai Huang ◽  
Yuli Wei ◽  
Shida Long ◽  
...  
Keyword(s):  
Pulmonary Fibrosis ◽  
Signaling Pathway ◽  
Transforming Growth Factor ◽  
Kinase Inhibitor ◽  
In Vivo Experiments ◽  
Age Related ◽  
And Migration ◽  
Tgf Β1

Idiopathic pulmonary fibrosis (IPF) is a fatal and age-related pulmonary disease. Nintedanib is a receptor tyrosine kinase inhibitor, and one of the only two listed drugs against IPF. Regorafenib is a novel, orally active, multi-kinase inhibitor that has similar targets to nintedanib and is applied to treat colorectal cancer and gastrointestinal stromal tumors in patients. In this study, we first identified that regorafenib could alleviate bleomycin-induced pulmonary fibrosis in mice. The in vivo experiments indicated that regorafenib suppresses collagen accumulation and myofibroblast activation. Further in vitro mechanism studies showed that regorafenib inhibits the activation and migration of myofibroblasts and extracellular matrix production, mainly through suppressing the transforming growth factor (TGF)-β1/Smad and non-Smad signaling pathways. In vitro studies have also indicated that regorafenib could augment autophagy in myofibroblasts by suppressing TGF-β1/mTOR (mechanistic target of rapamycin) signaling, and could promote apoptosis in myofibroblasts. In conclusion, regorafenib attenuates bleomycin-induced pulmonary fibrosis by suppressing the TGF-β1 signaling pathway.

scholarly journals Impact of Polyphenolic-Food on Longevity: An Elixir of Life. An Overview

Antioxidants ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 507
Author(s):  
Rosaria Meccariello ◽  
Stefania D’Angelo
Keyword(s):  
Oxidative Stress ◽  
Food Sources ◽  
Preventive Action ◽  
Nutritional Interventions ◽  
Beneficial Effects ◽  
Age Related ◽  
Macromolecular Damage ◽  
And Oxidative Stress

Aging and, particularly, the onset of age-related diseases are associated with tissue dysfunction and macromolecular damage, some of which can be attributed to accumulation of oxidative damage. Recently, growing interest has emerged on the beneficial effects of plant-based diets for the prevention of chronic diseases including obesity, diabetes, and cardiovascular disease. Several studies collectively suggests that the intake of polyphenols and their major food sources may exert beneficial effects on improving insulin resistance and related diabetes risk factors, such as inflammation and oxidative stress. They are the most abundant antioxidants in the diet, and their intake has been associated with a reduced aging in humans. Polyphenolic intake has been shown to be effective at ameliorating several age-related phenotypes, including oxidative stress, inflammation, impaired proteostasis, and cellular senescence, both in vitro and in vivo. In this paper, effects of these phytochemicals (either pure forms or polyphenolic-food) are reviewed and summarized according to affected cellular signaling pathways. Finally, the effectiveness of the anti-aging preventive action of nutritional interventions based on diets rich in polyphenolic food, such as the diets of the Blue zones, are discussed.

scholarly journals Complement C5 is not critical for the formation of sub-RPE deposits in Efemp1 mutant mice

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Donita L. Garland ◽  
Eric A. Pierce ◽  
Rosario Fernandez-Godino
Keyword(s):  
Macular Degeneration ◽  
Retinal Pigment ◽  
Age Related Macular Degeneration ◽  
Deposit Formation ◽  
Genetic Ablation ◽  
Age Related ◽  
Complement Dysregulation

AbstractThe complement system plays a role in the formation of sub-retinal pigment epithelial (RPE) deposits in early stages of age-related macular degeneration (AMD). But the specific mechanisms that connect complement activation and deposit formation in AMD patients are unknown, which limits the development of efficient therapies to reduce or stop disease progression. We have previously demonstrated that C3 blockage prevents the formation of sub-RPE deposits in a mouse model of EFEMP1-associated macular degeneration. In this study, we have used double mutant Efemp1R345W/R345W:C5-/- mice to investigate the role of C5 in the formation of sub-RPE deposits in vivo and in vitro. The data revealed that the genetic ablation of C5 does not eliminate the formation of sub-RPE deposits. Contrarily, the absence of C5 in RPE cultures promotes complement dysregulation that results in increased activation of C3, which likely contributes to deposit formation even in the absence of EFEMP1-R345W mutant protein. The results also suggest that genetic ablation of C5 alters the extracellular matrix turnover through an effect on matrix metalloproteinases in RPE cell cultures. These results confirm that C3 rather than C5 could be an effective therapeutic target to treat early AMD.

scholarly journals Phytochemical Study and In Vitro Screening Focusing on the Anti-Aging Features of Various Plants of the Greek Flora

Antioxidants ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 1206
Author(s):  
Aimilia D. Sklirou ◽  
Maria T. Angelopoulou ◽  
Aikaterini Argyropoulou ◽  
Eliza Chaita ◽  
Vasiliki Ioanna Boka ◽  
...  
Keyword(s):  
Plant Species ◽  
High Performance ◽  
High Resolution Mass Spectrometry ◽  
Ultra Performance Liquid Chromatography ◽  
Skin Aging ◽  
Rosa Damascena ◽  
Phytochemical Study ◽  
Age Related

Skin health is heavily affected by ultraviolet irradiation from the sun. In addition, senile skin is characterized by major changes in the collagen, elastin and in the hyaluronan content. Natural products (NPs) have been shown to delay cellular senescence or in vivo aging by regulating age-related signaling pathways. Moreover, NPs are a preferable source of photoprotective agents and have been proven to be useful against the undesirable skin hyperpigmentation. Greek flora harvests great plant diversity with approximately 6000 plant species, as it has a wealth of NPs. Here, we report an extensive screening among hundreds of plant species. More than 440 plant species and subspecies were selected and evaluated. The extracts were screened for their antioxidant and anti-melanogenic properties, while the most promising were further subjected to various in vitro and cell-based assays related to skin aging. In parallel, their chemical profile was analyzed with High-Performance Thin-Layer Chromatography (HPTLC) and/or Ultra-Performance Liquid Chromatography High-Resolution Mass Spectrometry (UPLC-HRMS). A variety of extracts were identified that can be of great value for the cosmetic industry, since they combine antioxidant, photoprotective, anti-melanogenic and anti-aging properties. In particular, the methanolic extracts of Sideritis scardica and Rosa damascena could be worthy of further attention, since they showed interesting chemical profiles and promising properties against specific targets involved in skin aging.

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