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 A Novel Synthesized Sulfonamido-Based Gallate-JEZTC Blocks Cartilage Degradation on Rabbit Model of Osteoarthritis: An in Vitro and in Vivo Study

2018 ◽  
Vol 49 (6) ◽  
pp. 2304-2319 ◽  
Author(s):  
Zhenhui Lu ◽  
Qin Liu ◽  
Lei Liu ◽  
Huayu Wu ◽  
Li Zheng ◽  
...  
Keyword(s):  
Signaling Pathways ◽  
Cruciate Ligament ◽  
Interleukin 1 ◽  
Rabbit Model ◽  
Cartilage Degradation ◽  
Tissue Inhibitor Of Metalloproteinase ◽  
Histological Evaluation ◽  
Chondrocyte Apoptosis

Background/Aims: 3, 4, 5-trihydroxy-N-{4-[(5-methylisoxazol-3-yl) sulfamoyl] phenyl} benzamide (JEZTC), synthesized from gallic acid (GA) and sulfamethoxazole (SMZ), was reported with chondroprotective effects. However, the effects of JEZTC on osteoarthritis (OA) are still unclear. The goal of this study was to investigate the anti-osteoarthritic properties of JEZTC on interleukin-1-beta (IL-1β) stimulated chondrocytes in vitro and a rabbit anterior cruciate ligament transaction (ACLT) OA model in vivo. Methods: Changes in matrix metalloproteinases (MMPs) and apoptosis genes (bax, caspase 3 and tnf-α) and OA-specific protein (MMP-1) expression in vitro and in vivo were detected by real-time quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and immunohistochemistry. The production of reactive oxygen species (ROS) were investigated upon the treatment of JEZTC in chondrocytes processed with IL-1β in vitro and OA in vivo. Effect of JEZTC on OA was further studied by the macroscopic and histological evaluation and scores. The key proteins in signaling pathways inMAPK/P38, PI3KAkt and NF-κB also determined using western blot (WB) analysis. Results: JEZTC could significantly suppress the expression of MMPs and intracellular ROS, while meaningfully increase the gene expression of tissue inhibitor of metalloproteinase-1 (TIMP-1). Moreover, there was less cartilage degradation in JEZTC group compared with the phosphate-buffered saline (PBS) group in vivo. Results also indicated that JEZTC exerts effect on OA by regulating MAPKs and PI3K/Akt signaling pathways to activate NF-κB pathway, leading to the down-regulation of MMPs. The chondro-protective effect of JEZTC may be related with its ability to inhibit chondrocyte apoptosis by reduction of ROS production. Conclusion: JEZTC may be a possible therapeutic agent in the treatment of OA.

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 Whether Sutures Reduce the Graft Laceration Caused by Interference Screw in Anterior Cruciate Ligament Reconstruction a Biomechanical Study in Vitro

2021 ◽  
Author(s):  
Yuanjun Teng ◽  
Lijun Da ◽  
Xiaohui Zhang ◽  
Hong Wang ◽  
Hua Han ◽  
...  
Keyword(s):  
Anterior Cruciate Ligament ◽  
Acl Reconstruction ◽  
Cruciate Ligament ◽  
Interference Screw ◽  
Biomechanical Study ◽  
Protective Effects ◽  
Mineral Density ◽  
Interference Screws ◽  
Anterior Cruciate

Abstract Background: Interference screw is commonly used for graft fixation in anterior cruciate ligament (ACL) reconstruction However, previous studies h a d reported that the insertion of interference screws significantly caused graft laceration . The purpose of this study was to determine whether sutures reduce d the graft laceration from the insertion of interference screws in ACL reconstruction. Methods: Porcine tibias and bovine extensor tendons were used for establishing a knee model of ACL reconstruction in vitro . The ends of grafts were sutured using three different sutures, including the bioabsorbable, Ethibond and ultra high molecular weight polyethylene (UHMWPE) sutures Poly ether ether ketone (PEEK) interference screw s w ere used fortibial fixation Biomechanical tests were performed to investigate the protective effects of different sutures on grafts Results : All prepared tendons and bone specimens showed similar characteristics (length, weight, and pre tension of the tendons, tibial bone mineral density) among all groups ( P 0.05). The biomechanical test s demonstrated that PEEK interference screw s significantly caused the graft laceration P 0.05). However, all sutures (the bioabsorbable, Ethibond and UHMWPE sutures) did not reduce the graft laceration in ACL reconstruction P 0.05). Conclusions : PEEK interference screw s significantly weakened the biomechanical properties of grafts during tibial fixation in ACL reconstruction. Absorbable Ethibond and UHMWPE sutures did not provide protective effects on grafts during ACL reconstruction.

scholarly journals Expression of LOXs and MMP-1, 2, 3 by ACL Fibroblasts and Synoviocytes Impact of Coculture and TNF-α

2018 ◽  
Vol 32 (04) ◽  
pp. 352-360 ◽  
Author(s):  
Chunli Wang ◽  
Qingjia Chi ◽  
Chunming Xu ◽  
Kang Xu ◽  
Yanjun Zhang ◽  
...  
Keyword(s):  
Cruciate Ligament ◽  
Cartilage Degradation ◽  
Ligament Injury ◽  
Tnf Α ◽  
Gene And Protein Expression ◽  
Polymerase Chain ◽  
Anterior Cruciate ◽  
Factor Α ◽  
First Time ◽  
Necrosis Factor

AbstractThis study aims to confirm the effects of synoviocytes (SCs) on regulating lysyl oxidases (LOXs) and matrix metalloproteinase (MMP)-1, 2, 3 in the normal and injured anterior cruciate ligament (ACL) fibroblasts response to tumor necrosis factor-α(TNF-α). The gene and protein expression levels of LOXs and MMP-1, 2, 3 in SCs cocultured ACL fibroblasts (ACLfs) induced by TNF-α and mechanical injury were analyzed by real-time polymerase chain reaction (PCR) and western bolting; the MMP-2 activity were analyzed by zymography. The results exhibited that TNF-α alone slightly downregulated the expressions of LOXs and upregulated the expression of MMP-1, 2, 3 in both normal and injured ACL fibroblasts. The decrease of LOXs and increase of MMP-1, 2, 3 in ACLfs response to TNF-α were further promoted by coculture. Taken together, these results show for the first time that the crosstalk between ACLfs and SCs could modulate the LOXs and MMP-1, 2, 3 synthesis in ACLfs in the presence of TNF-α. Accumulation of MMPs in the isolated fluid-containing space not only disrupts the balance of ACL healing, but also increases cartilage degradation and accelerates osteoarthritis (OA) in injured joint. Based on this mechanism, targeting inhibition of MMPs could provide a promising therapeutic strategy for acute ligament injury.

Finite Element Modelling of In Vitro Articular Cartilage Wear in the Patellofemoral Joint

2012 ◽  
Author(s):  
Lingmin Li ◽  
Shantanu Patil ◽  
Nick Steklov ◽  
Won Bae ◽  
Darryl D. D’Lima ◽  
...  
Keyword(s):  
Articular Cartilage ◽  
Cruciate Ligament ◽  
Computational Simulation ◽  
Knee Kinematics ◽  
Cartilage Degradation ◽  
Knee Oa ◽  
Cartilage Wear ◽  
Anterior Cruciate ◽  
A Site

The mechanism by which altered knee joint motions and loads (e.g., following anterior cruciate ligament (ACL) injury) contribute to the development of knee osteoarthritis (OA) is not well understood. One mechanobiological hypothesis is that articular cartilage degradation is initiated when altered knee kinematics increase loading on certain regions of the articular surfaces and decrease loading on other regions [1]. If homeostatic loading conditions vary from region to region, then load changes induced by altered kinematics could initiate cartilage degradation in a site-specific manner. This hypothesis is attractive from a computational simulation perspective since it is based on mechanical factors that lend themselves well to physical modeling. If computational simulations could predict the knee OA development process, then they could potentially be used to facilitate the design of new or improved treatments for the disease.

In-Vivo Force Estimation of the Anterior Cruciate Ligament

2009 ◽  
Author(s):  
Ali Hosseini ◽  
Thomas J. Gill ◽  
Guoan Li
Keyword(s):  
Anterior Cruciate Ligament ◽  
Cruciate Ligament ◽  
Acl Injury ◽  
Force Estimation ◽  
Non Invasive ◽  
Injury Mechanisms ◽  
Invasive Method ◽  
Anterior Cruciate

The knowledge of in-vivo ACL forces is instrumental for understanding ACL injury mechanisms and for improving surgical ACL reconstruction techniques. Several in-vitro investigations have measured ACL forces in response to various loads applied to the knee. However, in-vivo ACL forces in response to controlled loading are still unknown. The objective of this study was to estimate the force of healthy ACL as well as the possible upper bound of ACL forces under an increasing axial tibial loading in living subjects using a non-invasive method.

REGENERATION OF ANTERIOR CRUCIATE LIGAMENT WITH SILK-BASED SCAFFOLD IN PORCINE MODEL

2015 ◽  
Vol 15 (01) ◽  
pp. 1550006 ◽  
Author(s):  
ZHENG LI ◽  
JIANKANG HE ◽  
XIANG LI ◽  
WEIGUO BIAN ◽  
WENYOU ZHANG ◽  
...  
Keyword(s):  
Tissue Engineering ◽  
Anterior Cruciate Ligament ◽  
Porcine Model ◽  
Cruciate Ligament ◽  
Silk Fibers ◽  
Bone Interface ◽  
Anterior Cruciate ◽  
Large Animals

Silk was widely investigated as a promising scaffold material in ligament tissue engineering. Although a variety of silk scaffolds were developed for the regeneration of anterior cruciate ligament (ACL) in vitro and in vivo, more investigations should be performed in large animals to translate these findings into clinical applications. The aim of this study is to evaluate the feasibility of using silk-based ACL scaffolds to regenerate damaged ACLs in porcine model. The microstructural organization, tissue regeneration as well as ligament-bone interface of silk implants were evaluated with scanning electron microscopy, micro-computerized tomography, histological and immunohistochemical staining at three and six months postoperatively. The results demonstrated that silk fibers in the ACL scaffolds organized in parallel similar with collagen fibers in native ligaments, which facilitated and guided the penetration of newly regenerated tissue into the pores among silk fibers. Collagen production especially collagen I in silk implants significantly increased from three to six months, and was gradually close to the level of native ligaments. At implant-bone interface, indirect ligament-bone insertion was observed at three months and substantial Sharpey's fibers formed at six months. The results indicated that the silk-based ACL scaffold provides a promising tissue engineering approach for ACL regeneration.

Silk fibroin coating through EDC/NHS crosslink is an effective method to promote graft remodeling of a polyethylene terephthalate artificial ligament

2019 ◽  
Vol 33 (10) ◽  
pp. 1407-1414 ◽  
Author(s):  
Jiangyu Cai ◽  
Li Zhang ◽  
Jun Chen ◽  
Shiyi Chen
Keyword(s):  
Anterior Cruciate Ligament ◽  
Anterior Cruciate Ligament Reconstruction ◽  
Polyethylene Terephthalate ◽  
Silk Fibroin ◽  
Ligament Reconstruction ◽  
Cruciate Ligament ◽  
Cruciate Ligament Reconstruction ◽  
Anterior Cruciate

Anterior cruciate ligament reconstruction using polyethylene terephthalate artificial ligaments is one of the research hotspots in sports medicine but it is still challenging to achieve biological healing. The purpose of this study was to modify polyethylene terephthalate ligament with silk fibroin through ethyl-3–(3-dimethylaminopropyl)carbodiimide (EDC)/N-hydroxysuccinimide (NHS) crosslink and to investigate the performance of graft remodeling in vitro and in vivo. After silk fibroin coating, changes in the surface properties of ligament were characterized by scanning electron microscopy, attenuated total reflectance-Fourier transform infrared spectroscopy and water contact angle measurements. The compatibility of polyethylene terephthalate ligament with silk fibroin coating was investigated in vitro. The results showed the silk fibroin coating significantly improved adhesion, proliferation and extracellular matrix secretion of fibroblast cells. Moreover, a rabbit anterior cruciate ligament reconstruction model was established to evaluate the effect of ligament with silk fibroin coating in vivo. The gross observation and histological results showed that the silk fibroin coating significantly inhibited inflammation response and promoted new tissue regeneration with fusiform cells infiltration in and around the graft. Furthermore, the expressions of collagen I protein and mRNA in the silk fibroin-coated polyethylene terephthalate group were much higher than those in the control group according to the immunohistochemical and real-time polymerase chain reaction results. Therefore, silk fibroin coating through EDC/NHS crosslink promotes the biocompatibility and remodeling process of polyethylene terephthalate artificial ligament in vitro and in vivo. It can be considered as a potential solution to the problem of poor remodeling of artificial ligaments after anterior cruciate ligament reconstruction in the clinical applications.

Does Graft Construct Lengthening at the Fixations Cause an Increase in Anterior Laxity Following Anterior Cruciate Ligament Reconstruction in vivo?

2010 ◽  
Vol 132 (8) ◽  
Author(s):  
Conrad K. Smith ◽  
M. L. Hull ◽  
S. M. Howell
Keyword(s):  
Anterior Cruciate Ligament ◽  
Cruciate Ligament ◽  
Bone Tunnel ◽  
Anterior Cruciate Ligament Graft ◽  
Potential Increase ◽  
Anterior Laxity ◽  
Fresh Frozen ◽  
Anterior Cruciate

A millimeter-for-millimeter relation between an increase in length of an anterior cruciate ligament graft construct and an increase in anterior laxity has been demonstrated in multiple in vitro studies. Based on this relation, a 3 mm increase in length of the graft construct following surgery could manifest as a 3 mm increase in anterior laxity in vivo, which is considered clinically unstable. Hence, the two primary objectives were to determine whether the millimeter-for-millimeter relation exists in vivo for slippage-resistant fixation of a soft-tissue graft and, if it does not exist, then to what extent the increase in stiffness caused by biologic healing of the graft to the bone tunnel offsets the potential increase in anterior laxity resulting from lengthening at the sites of fixation. Sixteen subjects were treated with a fresh-frozen, nonirradiated, nonchemically processed tibialis allograft. Tantalum markers were injected into the graft, fixation devices, and bones. On the day of surgery and at 1, 2, 3, and 4 months, Roentgen stereophotogrammetric analysis was used to compute anterior laxity at 150 N of anterior force and the total slippage from both sites of fixation. A simple linear regression was performed to determine whether the millimeter-for-millimeter relation existed and a springs-in-series model of the graft construct was used to determine the extent to which the increase in stiffness caused by biological healing of the graft to the bone tunnel offset the increase in anterior laxity resulting from lengthening at the sites of fixation. There was no correlation between lengthening at the sites of fixation and the increase in anterior laxity at 1 month (R2=0.0, slope=0.2). Also, the increase in stiffness of the graft construct caused by biologic healing of the graft to the bone tunnel offset 0.7 mm of the 1.5 mm potential increase in anterior laxity resulting from lengthening at the sites of fixation. This relatively large offset of nearly 50% occurred because lengthening at the sites of fixation was small.

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