scholarly journals Ameliorative Effects of Loganin on Arthritis in Chondrocytes and Destabilization of the Medial Meniscus-Induced Animal Model

2021 ◽  
Vol 14 (2) ◽  
pp. 135
Author(s):  
Eunkuk Park ◽  
Chang Gun Lee ◽  
Seung Hee Yun ◽  
Seokjin Hwang ◽  
Hyoju Jeon ◽  
...  
Keyword(s):  
Matrix Metalloproteinase ◽  
Medial Meniscus ◽  
Bioactive Compound ◽  
Cartilage Degeneration ◽  
Cartilage Degradation ◽  
Protective Effects ◽  
Matrix Metalloproteinase 3 ◽  
Cox 2

Arthritis is a common inflammatory disease that causes pain, stiffness, and joint swelling. Here, we investigated the ameliorative effects of loganin on arthritis in vitro and in vivo. A single bioactive compound was fractionated and isolated from Cornus officinalis (CO) extract to screen for anti-arthritic effects. A single component, loganin, was identified as a candidate. The CO extract and loganin inhibited the expression of factors associated with cartilage degradation, such as cyclooxygenase-2 (COX-2), matrix metalloproteinase 3 (MMP-3), and matrix metalloproteinase 13 (MMP-13), in interukin-1 beta (IL-1β)-induced chondrocyte inflammation. In addition, prostaglandin and collagenase levels were reduced following treatment of IL-1β-induced chondrocytes with loganin. In the destabilization of the medial meniscus (DMM)-induced mouse model, loganin administration attenuated cartilage degeneration by inhibiting COX-2, MMP-3, and MMP-13. Transverse micro-CT images revealed that loganin reduced DMM-induced osteophyte formation. These results indicate that loganin has protective effects in DMM-induced mice.

scholarly journals Antiosteoarthritic Effect of Morroniside in Chondrocyte Inflammation and Destabilization of Medial Meniscus-Induced Mouse Model

2021 ◽  
Vol 22 (6) ◽  
pp. 2987
Author(s):  
Eunkuk Park ◽  
Chang Gun Lee ◽  
Seong Jae Han ◽  
Seung Hee Yun ◽  
Seokjin Hwang ◽  
...  
Keyword(s):  
Matrix Metalloproteinase ◽  
Medial Meniscus ◽  
Interleukin 1 ◽  
Bioactive Compound ◽  
Joint Inflammation ◽  
Cartilage Degradation ◽  
Cartilage Destruction ◽  
Raw 264.7 Cells ◽  
Potential Candidate ◽  
Cox 2

Osteoarthritis (OA) is a common degenerative disease that results in joint inflammation as well as pain and stiffness. A previous study has reported that Cornus officinalis (CO) extract inhibits oxidant activities and oxidative stress in RAW 264.7 cells. In the present study, we isolated bioactive compound(s) by fractionating the CO extract to elucidate its antiosteoarthritic effects. A single bioactive component, morroniside, was identified as a potential candidate. The CO extract and morroniside exhibited antiosteoarthritic effects by downregulating factors associated with cartilage degradation, including cyclooxygenase-2 (Cox-2), matrix metalloproteinase 3 (Mmp-3), and matrix metalloproteinase 13 (Mmp-13), in interleukin-1 beta (IL-1β)-induced chondrocytes. Furthermore, morroniside prevented prostaglandin E2 (PGE2) and collagenase secretion in IL-1β-induced chondrocytes. In the destabilization of the medial meniscus (DMM)-induced mouse osteoarthritic model, morroniside administration attenuated cartilage destruction by decreasing expression of inflammatory mediators, such as Cox-2, Mmp3, and Mmp13, in the articular cartilage. Transverse microcomputed tomography analysis revealed that morroniside reduced DMM-induced sclerosis in the subchondral bone plate. These findings suggest that morroniside may be a potential protective bioactive compound against OA pathogenesis.

scholarly journals RETRACTED ARTICLE: Chondro-protective effects of polydatin in osteoarthritis through its effect on restoring dysregulated autophagy via modulating MAPK, and PI3K/Akt signaling pathways

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Zhengyuan Wu ◽  
Zhiwei Luan ◽  
Xiaohan Zhang ◽  
Kai Zou ◽  
Shiting Ma ◽  
...  
Keyword(s):  
Signaling Pathways ◽  
Cartilage Degeneration ◽  
Cartilage Degradation ◽  
Akt Signaling ◽  
Protective Effects ◽  
Mediating Role ◽  
Retracted Article ◽  
Underlying Mechanisms

Abstract Osteoarthritis (OA) is a degenerative disease of the cartilage that is prevalent in the middle-aged and elderly demography. Polydatin (PD), a natural resveratrol glucoside, has shown significant anti-inflammatory and anti-arthritic potential in previous studies. This study was designed to evaluate the therapeutic properties of PD in vitro and in vivo, and elucidate their underlying mechanisms. The expression levels of all relevant factors were evaluated by qRT-PCR, western blotting, and immunohistochemistry (IHC) where suitable. Reactive oxygen species (ROS) and apoptosis were analyzed using the suitable probes and flow cytometry. The histological evidence of cartilage was assessed in rat models, moreover, the several serum cytokines levels and autophagy levels were evaluated. The result showed PD displayed significant chondro-protective effects, inferred in terms of reduced inflammation and cartilage degradation, apoptosis inhibition, and lower ROS production. The protective effects were attenuated by the autophagy inhibitor 3-MA, indicating a mediating role of autophagy in PD action. Mechanistically, PD exerted its effects by inhibiting the MAPK and PI3K/Akt signaling pathways which led to the down-regulation of mTOR. In conclusion, PD protects against cartilage degeneration by activating the autophagy flux in the chondrocytes via the MAPK and PI3K/Akt signaling pathways.

scholarly journals Vaspin Alleviates Osteoarthritis by Inhibiting NLRP3-mediated Inflammation

2021 ◽  
Author(s):  
Xianjie Zhu ◽  
Shiyou Dai ◽  
Baohua Xia ◽  
Jianbao Gong ◽  
Bingzheng Ma
Keyword(s):  
Nlrp3 Inflammasome ◽  
Wistar Rat ◽  
Cartilage Degradation ◽  
Pathological Process ◽  
Inflammasome Activation ◽  
Protective Effects ◽  
Collagen Formation ◽  
Nlrp3 Inflammasome Activation

Abstract Background:Osteoarthritis (OA) is a chronic degenerative joint bone disease characterized by cartilage degradation. Visceral adipose tissue-derived serine protease inhibitor (vaspin) is associated with the inflammatory and metabolic responses to OA. However, the underlying mechanisms of the pathological process of OA are not clear. The aim of the present study was to examine the protective effects of vaspin both in vitro and in vivo.Methods:Monosodium iodoacetate (MIA)-induced Wistar rat model of OA was used to assess the in vivo effects of vaspin administered for 12 weeks. The characteristics of OA were evaluated by haematoxylin and eosin (H&E) and safranin O/fast green staining. The anti-inflammatory effect of vaspin was assessed using immunohistochemical, qRT-PCR, and western blotting analysis. Parallel experiments to detect the molecular mechanism through which vaspin prevents OA were performed using LPS-treated chondrocytes.Results:Our results showed that the degeneration of cartilage and upregulated expression of matrix metalloproteinase (MMP)-1 and MMP-13 were ameliorated by vaspin. Additionally, vaspin suppressed the activation of TXNIP/NLRP3 and secretion of tumor necrosis factor ɑ and interleukin-1β in vivo. It was further confirmed that vaspin could also suppress LPS-induced NLRP3 inflammasome activation and reduce collagen formation in chondrocytes. Moreover, vaspin inhibited NLRP3 inflammasome activation by suppressing the ROS/TXNIP pathway.Conclusions: Vaspin inhibited OA by repressing TXNIP/NLRP3 activation in in vitro and in vivo models of OA, thus providing a novel therapeutic strategy for OA.

scholarly journals Protective Effects of 6-(Methylsulfinyl)hexyl Isothiocyanate on Aβ1-42-Induced Cognitive Deficit, Oxidative Stress, Inflammation, and Apoptosis in Mice

2018 ◽  
Vol 19 (7) ◽  
pp. 2083 ◽  
Author(s):  
Fabiana Morroni ◽  
Giulia Sita ◽  
Agnese Graziosi ◽  
Eleonora Turrini ◽  
Carmela Fimognari ◽  
...  
Keyword(s):  
Bioactive Compound ◽  
Biological Properties ◽  
Neuroprotective Activity ◽  
Inflammatory Factors ◽  
Protective Effects ◽  
Behavioral Recovery ◽  
Memory Impairments ◽  
Wasabia Japonica

Alzheimer’s disease (AD) is the most common form of dementia among older people. Although soluble amyloid species are recognized triggers of the disease, no therapeutic approach is able to stop it. 6-(Methylsulfinyl)hexyl isothiocyanate (6-MSITC) is a major bioactive compound in Wasabia japonica, which is a typical Japanese pungent spice. Recently, in vivo and in vitro studies demonstrated that 6-MSITC has several biological properties. The aim of the present study was to investigate the neuroprotective activity of 6-MSITC in a murine AD model, induced by intracerebroventricular injection of β-amyloid oligomers (Aβ1-42O). The treatment with 6-MSITC started 1 h after the surgery for the next 10 days. Behavioral analysis showed that 6-MSITC ameliorated Aβ1-42O-induced memory impairments. The decrease of glutathione levels and increase of reactive oxygen species in hippocampal tissues following Aβ1-42O injection were reduced by 6-MSITC. Moreover, activation of caspases, increase of inflammatory factors, and phosphorylation of ERK and GSK3 were inhibited by 6-MSITC. These results highlighted an interesting neuroprotective activity of 6-MSITC, which was able to restore a physiological oxidative status, interfere positively with Nrf2-pathway, decrease apoptosis and neuroinflammation and contribute to behavioral recovery. Taken together, these findings demonstrated that 6-MSITC could be a promising complement for AD therapy.

scholarly journals Study of Osteoarthritis Treatment with Anti-Inflammatory Drugs: Cyclooxygenase-2 Inhibitor and Steroids

2015 ◽  
Vol 2015 ◽  
pp. 1-10 ◽  
Author(s):  
Hongsik Cho ◽  
Andrew Walker ◽  
Jeb Williams ◽  
Karen A. Hasty
Keyword(s):  
Gene Expression ◽  
Type Ii Collagen ◽  
Cartilage Degradation ◽  
Cyclooxygenase 2 ◽  
Cox Inhibitor ◽  
Inflammatory Drugs ◽  
Cox 2 ◽  
Anti Inflammatory

Patients with osteoarthritis (OA), a condition characterized by cartilage degradation, are often treated with steroids, nonsteroidal anti-inflammatory drugs (NSAIDs), and cyclooxygenase-2 (COX-2) selective NSAIDs. Due to their inhibition of the inflammatory cascade, the drugs affect the balance of matrix metalloproteinases (MMPs) and inflammatory cytokines, resulting in preservation of extracellular matrix (ECM). To compare the effects of these treatments on chondrocyte metabolism, TNF-αwas incubated with cultured chondrocytes to mimic a proinflammatory environment with increasing production of MMP-1 and prostaglandin E2 (PGE2). The chondrocytes were then treated with either a steroid (prednisone), a nonspecific COX inhibitor NSAID (piroxicam), or a COX-2 selective NSAID (celecoxib). Both prednisone and celecoxib decreased MMP-1 and PGE-2 production while the nonspecific piroxicam decreased only the latter. Both prednisone and celecoxib decreased gene expression of MMP-1 and increased expression of aggrecan. Increased gene expression of type II collagen was also noted with celecoxib. The nonspecific piroxicam did not show these effects. The efficacy of celecoxibin vivowas investigated using a posttraumatic OA (PTOA) mouse model.In vivo, celecoxib increases aggrecan synthesis and suppresses MMP-1. In conclusion, this study demonstrates that celecoxib and steroids exert similar effects on MMP-1 and PGE2 productionin vitroand that celecoxib may demonstrate beneficial effects on anabolic metabolismin vivo.

The Protective Effect of Kirenol in Osteoarthritis: an in Vitro and in Vivo Study

2022 ◽  
Author(s):  
Wei Hu ◽  
Chao Mao ◽  
Weibin Sheng
Keyword(s):  
Cartilage Degradation ◽  
Cartilage Destruction ◽  
In Vivo Study ◽  
Griess Reaction ◽  
Tnf Α ◽  
Collagen Ii ◽  
Cox 2 ◽  
Product Compound

Abstract Background: Osteoarthritis (OA) is a chronic degenerative disease, its main characteristic involves articular cartilage destruction and inflammation response, absent of effective medical treatment. Our current research aimed to explore anti-inflammatory effect of kirenol, a diterpenoid natural product compound, in the development of OA and its potential molecular mechanism through in vitro and in vivo study.Methods: In vitro, chondrocytes were pretreated with kirenol for 2 h before IL-1β stimulation. Production of NO, PGE2, TNF-α, IL-6, aggrecan, collagen-II, MMP13and ADAMTS5 were evaluated by the Griess reaction and ELISAs. The mRNA (aggrecan and collagen-II) and protein expression (COX-2, iNOS, P65, IκB, PI3K, AKT) were measured by qRT-PCR and Western blot respectively. Immunofluorescence was used to assess the expression of collagen-II and P65. The in vivo effect of kirenol was evaluated in mice OA models induced by destabilization of the medial meniscus (DMM).Results: We found that kirenol inhibited IL-1β-induced expression of NO, PGE2, TNF-α, IL-6, COX-2, iNOS, ADAMTS-5. Besides, kirenol remarkably decreased IL-1β-induced degradation of aggrecan and collagen-II. Furthermore, kirenol significantly inhibited IL-1β-induced phosphorylation of PI3K/Akt and NF-κB signaling. In vivo, the cartilage in kirenol-treated mice exhibited less cartilage degradation and lower OARSI scores.Conclusions: Taken together, the results of this study provide potent evidence that kirenol could be utilized as a potentially therapeutic agent in prevention and treatment of OA.

Danshen attenuates osteoarthritis-related cartilage degeneration through inhibition of NF-κB signaling pathway in vivo and in vitro

2017 ◽  
Vol 95 (6) ◽  
pp. 644-651 ◽  
Author(s):  
Xilin Xu ◽  
Hang Lv ◽  
Xiaodong Li ◽  
Hui Su ◽  
Xiaofeng Zhang ◽  
...  
Keyword(s):  
Matrix Metalloproteinase ◽  
Signaling Pathway ◽  
Salvia Miltiorrhiza ◽  
B Cell Lymphoma ◽  
Cartilage Degeneration ◽  
Nuclear Accumulation ◽  
Therapeutic Effects ◽  
Osteoarthritic Cartilage

Danshen (Salvia miltiorrhiza) is a traditional Chinese medicine herb that can alleviate the symptoms of osteoarthritis (OA) (Söder et al. 2006) in animals. However, the underlying mechanisms remain poorly understood and require further investigation. In this study, rabbits with experimentally induced OA were given an intra-articular injection of danshen (0.7 mL/day) for 5 weeks. In addition to attenuating the cartilage degeneration of OA in the rabbits, danshen decreased the expression and activity of matrix metalloproteinase 9 (MMP-9) and MMP-13, and increased the expression of their natural inhibitors: tissue inhibitor of matrix metalloproteinase 1 (TIMP-1) and TIMP-2. Apoptosis in osteoarthritic cartilage tissues was attenuated by danshen, accompanied with increased expression of B cell lymphoma 2 (Bcl-2) and decreased levels of Bcl-2-associated X protein (Bax). Further, danshen inhibited the nuclear accumulation of nuclear factor kappa-B (NF-κB) p65 in osteoarthritic cartilage. The therapeutic effects of danshen in vivo were comparable to that of sodium hyaluronate, which is a drug used clinically for the treatment OA. In vitro, sodium nitroprusside (SNP) was used to stimulate apoptosis in primary rabbit chondrocytes. We found that the SNP-induced apoptosis was mitigated by danshen. BAY11-7028, an inhibitor of the NF-κB pathway, augmented danshen’s anti-apoptotic effects in cells exposed to SNP. When these results are considered together, they indicate that danshen alleviates the cartilage injury in rabbit OA through inhibition of the NF-κB signaling pathway.

scholarly journals Galectin network in osteoarthritis: galectin-4 programs a pathogenic signature of gene and effector expression in human chondrocytes in vitro

2021 ◽  
Author(s):  
Katharina M. Pichler ◽  
Anita Fischer ◽  
Jürgen Alphonsus ◽  
Catharina Chiari ◽  
Sebastian Schmidt ◽  
...  
Keyword(s):  
Matrix Metalloproteinase ◽  
Cartilage Degradation ◽  
Cross Linking ◽  
Transcriptome Data ◽  
Matrix Metalloproteinase 13 ◽  
Carbohydrate Recognition Domains ◽  
Inflammatory Proteins ◽  
Oa Chondrocytes

AbstractGalectin-4 (Gal-4) is a member of the galectin family, which have been identified as galactose-binding proteins. Gal-4 possesses two tandem repeat carbohydrate recognition domains and acts as a cross-linking bridge in sulfatide-dependent glycoprotein routing. We herein document its upregulation in osteoarthritis (OA) in correlation with the extent of cartilage degradation in vivo. Primary human OA chondrocytes in vitro respond to carbohydrate-inhibitable Gal-4 binding with the upregulation of pro-degradative/-inflammatory proteins such as interleukin-1β (IL-1β) and matrix metalloproteinase-13 (MMP-13), as documented by RT-qPCR-based mRNA profiling and transcriptome data processing. Activation of p65 by phosphorylation of Ser536 within the NF-κB pathway and the effect of three p65 inhibitors on Gal-4 activity support downstream involvement of such signaling. In 3D (pellet) cultures, Gal-4 presence causes morphological and biochemical signs of degradation. Taken together, our findings strongly support the concept of galectins acting as a network in OA pathogenesis and suggest that blocking their activity in disease progression may become clinically relevant in the future.

scholarly journals Tetrandrine Inhibits the Wnt/β-Catenin Signalling Pathway and Alleviates Osteoarthritis: An In Vitro and In Vivo Study

2013 ◽  
Vol 2013 ◽  
pp. 1-8 ◽  
Author(s):  
Xindie Zhou ◽  
Weijun Li ◽  
Lifeng Jiang ◽  
Jiapeng Bao ◽  
Lijiang Tao ◽  
...  
Keyword(s):  
Cruciate Ligament ◽  
Cartilage Degradation ◽  
Signalling Pathway ◽  
Tissue Inhibitor Of Metalloproteinase ◽  
Protective Effects ◽  
Transaction Model ◽  
Polymerase Chain ◽  
Anterior Cruciate

There is currently no effective drug treatment for the early phase of osteoarthritis (OA), one of the most common senile diseases. The goal of this study was to investigate the protective effect of the tetrandrine (Tet) on OA, in vitro and in vivo. In an in vitro experiment, quantitative real-time polymerase chain reaction (qRT-PCR) was used to investigate changes in gene expression upon the addition of Tet in chondrocytes processed with IL-1β; changes in protein profiles were assessed by Western blotting. In vivo, to determine whether Tet has the protective effects on articular cartilage, a rabbit anterior cruciate ligament transaction model of OA was established. Expression of matrix metalloproteinase andβ-catenin genes increased significantly, while that of tissue inhibitor of metalloproteinase-1 decreased significantly in the OA group both in vivo and in chondrocytes. However, the changes of expression were reversed by Tet, and there was less cartilage degradation in vivo compared with the OA group, as assessed by histological and macroscopic observations. Thus, Tet may play a useful role in the treatment of OA through the Wnt/β-catenin signalling pathway and has potential for the treatment of OA.

scholarly journals The Role of MicroRNA-381 in Chondrogenesis and Interleukin-1-β Induced Chondrocyte Responses

2015 ◽  
Vol 36 (5) ◽  
pp. 1753-1766 ◽  
Author(s):  
Changhe Hou ◽  
Fangang Meng ◽  
Zhiqi Zhang ◽  
Yan Kang ◽  
Weishen Chen ◽  
...  
Keyword(s):  
Interleukin 1 ◽  
Type Ii Collagen ◽  
Cartilage Degeneration ◽  
Cartilage Degradation ◽  
Luciferase Assay ◽  
Type Ii ◽  
Osteoarthritic Cartilage ◽  
Enhanced Expression

Aim: The molecular pathways regulating cartilage degradation are unclear. miR-381 was identified as a putative regulator of chondrogenesis related genes. Here, we examined its role in chondrogenesis and osteoarthritic cartilage degeneration. Methods: miR-381 expression was assessed in vitro in response to IL-1β stimulation in primary human (PHC) and mouse (PMC) chondrocytes, and ATDC5 derived chondrocytes; and in vivo in mouse embryos and human osteoarthritic cartilage. The effects of miR-381 on chondrogenesis and NF-kB signaling were assessed using a synthetic RNA mimic or inhibitor and luciferase assay, respectively. Upstream regulators of miR381 were probed using siRNA or overexpression plasmids for Sox9 and Runx2. Results: miR-381 expression was elevated in chondrogenic and hypertrophic ATDC5 cells. miR-381 was induced in vitro by IL-1β in ATDC5 cells, PMCs, and PHCs, and was expressed in areas of cartilage degradation or absorption in vivo. Overexpression of Runx2 or Sox9 increased miR-381 expression in ATDC5 cells. miR-381 suppressed expression of collagen, type II, alpha 1, and enhanced expression of metalloproteinase-13 (MMP-13), but did not regulate NFKBIA and NKRF activity. Conclusion: miR-381 was highly expressed during chondrogenesis and in arthritic cartilage. It may contribute to absorption of the cartilage matrix by repressing type II collagen and inducing MMP-13.

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