scholarly journals PARP-1 inhibition attenuates the inflammatory response in the cartilage of a rat model of osteoarthritis

2021 ◽  
Vol 10 (7) ◽  
pp. 401-410
Author(s):  
Zili Liu ◽  
Honglin Wang ◽  
Shaoqian Wang ◽  
Jie Gao ◽  
Lei Niu
Keyword(s):  
Inflammatory Response ◽  
Knee Joint ◽  
Rat Model ◽  
Lentiviral Vector ◽  
Cruciate Ligament ◽  
Weight Bearing ◽  
Enzyme Linked Immunosorbent Assay ◽  
Medial Meniscectomy ◽  
Joint Width ◽  
Parp 1

Aims Poly (ADP-ribose) polymerase (PARP) inhibitor has been reported to attenuate inflammatory response in rat models of inflammation. This study was designed to investigate the effect of PARP signalling in osteoarthritis (OA) cartilage inflammatory response in an OA rat model. Methods The OA model was established by anterior cruciate ligament transection with medial meniscectomy in Wistar rats. The poly (ADP-ribose) polymerase 1 (PARP-1) shRNA (short hairpin (sh)-PARP-1) and negative control shRNA (sh-NC) were delivered using a lentiviral vector and were intra-articularly injected into rats after surgery. The weight-bearing distribution of the hind limbs and the knee joint width were measured every two weeks. The expression levels of PARP-1, inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2) in cartilage were determined using real-time quantitative reverse transcription polymerase chain reaction (RT-qPCR) and Western blot. The serum concentrations of inflammatory cytokines were detected using enzyme-linked immunosorbent assay (ELISA). Results PARP-1 expression level significantly increased in the cartilage of the established OA rat model. sh-PARP-1 treatment suppressed PARP-1 levels, decreased the Δ Force (the difference between the weight on ipsilateral limb and contralateral limb) and the knee joint width, inhibited cartilage matrix catabolic enzymes, and ameliorated OA cartilage degradation and attenuated inflammatory response. Conclusion PARP-1 inhibition attenuates OA cartilage inflammatory response in the OA rat model. Cite this article: Bone Joint Res 2021;10(7):401–410.

A Novel Joint Loading System to Investigate the Effect of Daily Mechanical Load on a Healing Anterior Cruciate Ligament (ACL) Reconstruction

2009 ◽  
Author(s):  
Mark Stasiak ◽  
Peter Torzilli ◽  
Carl Imhauser ◽  
Jonathan Packer ◽  
Asheesh Bedi ◽  
...  
Keyword(s):  
Anterior Cruciate Ligament ◽  
Knee Joint ◽  
Acl Reconstruction ◽  
Rat Model ◽  
Mechanical Load ◽  
Cruciate Ligament ◽  
Joint Distraction ◽  
The Us ◽  
Loading System ◽  
Anterior Cruciate

A novel system was developed to investigate the effect of mechanical load on tendon to bone healing, using a rat model of ACL reconstruction. A greater understanding of the effects of mechanical load may improve rehabilitation practices for the more than 100,000 ACL reconstructions each year in the US alone.[1] The purpose of this study was to assess: the accuracy of knee joint distraction, variability in fixator compliance, and ability of animals to tolerate the fixator over a typical loading protocol.

scholarly journals Ulinastatin improves renal microcirculation by protecting endothelial cells and inhibiting autophagy in a septic rat model

2022 ◽  
Author(s):  
Tian Li ◽  
Xiaojun Ji ◽  
Jingfeng Liu ◽  
Xinjie Guo ◽  
Ran Pang ◽  
...  
Keyword(s):  
Inflammatory Response ◽  
Rat Model ◽  
Cecal Ligation ◽  
Kidney Tissue ◽  
Kidney Injury ◽  
Inflammatory Factors ◽  
Enzyme Linked Immunosorbent Assay ◽  
Sprague Dawley ◽  
Male Adult ◽  
Renal Microcirculation

Introduction: Increased permeability of the renal capillaries is a common consequence of sepsis-associated acute kidney injury. Vascular endothelial (VE)-cadherin is a strictly endothelial-specific adhesion molecule that can control the permeability of the blood vessel wall. Additionally, autophagy plays an important role in maintaining cell stability. Ulinastatin, a urinary trypsin inhibitor, attenuates the systemic inflammatory response and visceral vasopermeability. However, it is uncertain whether ulinastatin can improve renal microcirculation by acting on the endothelial adhesion junction. Methods: We observed the effect of ulinastatin in a septic rat model using contrast-enhanced ultrasonography (CEUS) to evaluate the perfusion of the renal cortex and medulla. Male adult Sprague-Dawley rats were subjected to cecal ligation and puncture and divided into the sham, sepsis, and ulinastatin groups. Ulinastatin (50,000 U/kg) was injected into the tail vein immediately after the operation. The CEUS was performed to evaluate the renal microcirculation perfusion at 3, 6, 12, and 24 hours after the operation. Histological staining was used to evaluate kidney injury scores. Western blot (WB) was used to quantify the expression of VE-cadherin, LC3II, and inflammatory factors [interleukin -1β (IL-1β), interleukin -6 (IL-6), and tumor necrosis factor-α (TNF-α)] in kidney tissue, and enzyme-linked immunosorbent assay (ELISA) detected serum inflammatory factors and kidney function and early kidney injury biomarker levels. Results: Compared with the sham group, ulinastatin reduced the inflammatory response, inhibited autophagy, maintained the expression of VE-cadherin, and meliorated cortical and medullary perfusion. Conclusion: Ulinastatin effectively protects the adhesion junction and helps ameliorate the perfusion of kidney capillaries during sepsis by the inhibition of autophagy and the expression of inflammatory factors.

scholarly journals Effect of Fucoidan on Anterior Cruciate Ligament Transection and Medial Meniscectomy Induced Osteoarthritis in High-Fat Diet-Induced Obese Rats

2018 ◽  
Author(s):  
Sabri Sudirman ◽  
Alan Darmasaputra Ong ◽  
Heng-Wei Chang ◽  
Zwe-Ling Kong
Keyword(s):  
Anterior Cruciate Ligament ◽  
Cholesterol Level ◽  
High Fat Diet ◽  
Cruciate Ligament ◽  
Weight Bearing ◽  
Hdl Cholesterol ◽  
High Fat ◽  
Anterior Cruciate Ligament Transection ◽  
Medial Meniscectomy ◽  
Anterior Cruciate

Osteoarthritis (OA) has become one of the most common disabilities among elders, especially in female. Obesity and mechanical injury causing OA are attributed to joint loading, cartilage disintegration, bone loss and inflammation as well. Several strategies used for treatment OA including non-pharmacological and pharmacological. Fucoidan possesses several bioactivities such as antitumor, antiviral, anticoagulation, anti-obesity, and immunomodulation. This study aims to investigate the effect of fucoidan in surgery-induced OA on diet-induced obesity rats. OA was induced by anterior cruciate ligament transection and partial medial meniscectomy (ACLT+MMx). Male SD rats were fed high-fat diet (HFD) for 4 weeks to induce obesity before ACLT+MMx to induce OA. OA rats were administered with intragastric water or fucoidan in three different concentrations (32 mg/kg, 64 mg/kg, and 320 mg/kg) after the surgeries for 40 days with HFD. We observed that the swelling in knee joint was alleviated and hind paw weight distribution was rectified after feeding fucoidan, with no significant effect on weight gain and feed intake. Fucoidan administration indicated no significant variation on HDL-Cholesterol level, but reduced plasma triglycerides and LDL-Cholesterol level. In addition, weight-bearing tests showed improvement in the fucoidan-treated group. Our results suggested that fucoidan may improve meniscal/ligamentous injury and obesity-induced OA.

scholarly journals Effect of Fucoidan on Anterior Cruciate Ligament Transection and Medial Meniscectomy Induced Osteoarthritis in High-Fat Diet-Induced Obese Rats

2018 ◽  
Author(s):  
Sabri Sudirman ◽  
Alan Darmasaputra Ong ◽  
Heng-Wei Chang ◽  
Zwe-Ling Kong
Keyword(s):  
Anterior Cruciate Ligament ◽  
Cholesterol Level ◽  
High Fat Diet ◽  
Cruciate Ligament ◽  
Weight Bearing ◽  
Hdl Cholesterol ◽  
High Fat ◽  
Anterior Cruciate Ligament Transection ◽  
Medial Meniscectomy ◽  
Anterior Cruciate

Osteoarthritis (OA) has become one of the most common disabilities among elders, especially in female. Obesity and mechanical injury causing OA are attributed to joint loading, cartilage disintegration, bone loss and inflammation as well. Several strategies used for treatment OA including non-pharmacological and pharmacological. Fucoidan possesses several bioactivities such as antitumor, antiviral, anticoagulation, anti-obesity, and immunomodulation. This study aims to investigate the effect of fucoidan in surgery-induced OA on diet-induced obesity rats. OA was induced by anterior cruciate ligament transection and partial medial meniscectomy (ACLT+MMx). Male SD rats were fed high-fat diet (HFD) for 4 weeks to induce obesity before ACLT+MMx to induce OA. OA rats were administered with intragastric water or fucoidan in three different concentrations (32 mg/kg, 64 mg/kg, and 320 mg/kg) after the surgeries for 40 days with HFD. We observed that the swelling in knee joint was alleviated and hind paw weight distribution was rectified after feeding fucoidan, with no significant effect on weight gain and feed intake. Fucoidan administration indicated no significant variation on HDL-Cholesterol level, but reduced plasma triglycerides and LDL-Cholesterol level. In addition, weight-bearing tests showed improvement in the fucoidan-treated group. Our results suggested that fucoidan may improve meniscal/ligamentous injury and obesity-induced OA.

COMPARATIVE ANALYSIS OF KNEE MUSCLE DAMAGE OF DIFFERENT ATHLETES

2021 ◽  
Vol 27 (7) ◽  
pp. 692-694
Author(s):  
Yanfei Yu ◽  
Huijun Yan
Keyword(s):  
Knee Joint ◽  
Cruciate Ligament ◽  
Weight Bearing ◽  
Sports Injury ◽  
Extensor Muscle ◽  
Level Of Evidence ◽  
Specific Strength ◽  
Extension Force ◽  
Knee Muscle

ABSTRACT Introduction: The knee joint is the most complex weight-bearing joint in the human body. An athlete's knee joint is prone to injury in competitive sports; it is one of the most common injuries and, in some sports, severe meniscus and cruciate ligament injuries occur frequently as, for example, in handball and soccer, and can even end the career of an elite athlete. Objective: To explore the comparison of knee flexion and extension force injury in different athletes. Methods: The characteristics of the flexor and extensor muscle of the knee joint in handball, football and cycling were studied with the isokinetic technique. Results: The role of the knee joint in different types of sports played by athletes is obviously different, which leads to the different requirements of the flexor and extensor muscle in the knee joint. Conclusions: The key to improving the conditions of superior strength and preventing sports injury is to develop the features of specific strength reasonably. Level of evidence II; Therapeutic studies - investigation of treatment results.

miR-29b is Involved in Cartilage Autophagy and Muscle Atrophy in a Rat Model of Knee Osteoarthritis

2020 ◽  
Author(s):  
Che Ji ◽  
Jia Peiyu ◽  
Ma Yantao ◽  
Han Qi ◽  
Wang Xiaolei ◽  
...  
Keyword(s):  
Anterior Cruciate Ligament ◽  
Knee Osteoarthritis ◽  
Therapeutic Effect ◽  
Muscle Atrophy ◽  
Rat Model ◽  
Cruciate Ligament ◽  
Weight Bearing ◽  
Periodic Acid ◽  
Anterior Cruciate Ligament Transection ◽  
Anterior Cruciate

Abstract Background Knee osteoarthritis (KOA) is a progressively degenerative form of arthritis characterized by chondrocyte apoptosis and cartilage degeneration. KOA also involves limb muscle atrophy, especially in the quadriceps muscles. However, there are limited options for the treatment of KOA. miR-29b stimulates apoptosis in the chondrocytes from patients with KOA and muscle atrophy in other models. Therefore, we investigated the therapeutic effect of miR-29b in cartilage autophagy and muscle atrophy. Methods Ten rats comprised the control cohort without anterior cruciate ligament transection. The treatment group (KOA induced in the right knee via anterior cruciate ligament transection) was divided into a model untreated group and a miR-29b-antagomir group (miR-29b antagomir injected 1 wk before surgery). Results Real-time polymerase chain reaction revealed successful downregulation of miR-29b using antagomir in the joints and muscles. A weight-bearing test showed that miR-29b downregulation affected joint function. Enzyme-linked immunosorbent assays demonstrated that downregulating miR-29b reduced pro-inflammatory cytokine expression. Immunohistochemistry revealed that miR-29b depletion enhanced autophagy by activating LC3 and beclin-1 in the cartilage. Autophagy was stimulated by the activation of MAPK and mTOR signaling. Depletion of miR-29b ameliorated the decrease in the weight of the quadriceps and the quadriceps weight/body weight ratio of the rats. Hematoxylin–eosin and periodic acid–Schiff staining showed that miR-29b downregulation inhibited muscular atrophy. Immunofluorescence showed that miR-29b downregulation affected IGF/PI3K/AKT signaling. Conclusions This study demonstrated the therapeutic effect of miR-29b on autophagy in the cartilage and on muscle atrophy in a rat model for KOA, highlighting the potential of miR-29b as a therapeutic target for KOA.

scholarly journals Effects of Dipsacus asperoides and Phlomis umbrosa Extracts in a Rat Model of Osteoarthritis

Plants ◽  
2021 ◽  
Vol 10 (10) ◽  
pp. 2030
Author(s):  
Jin Mi Chun ◽  
A Yeong Lee ◽  
Byeong Cheol Moon ◽  
Goya Choi ◽  
Joong-Sun Kim
Keyword(s):  
Knee Joint ◽  
Rat Model ◽  
Weight Bearing ◽  
Similar Efficacy ◽  
Herbal Products ◽  
Korean Medicine ◽  
Histopathological Features ◽  
Serum Cytokines ◽  
Monosodium Iodoacetate ◽  
Model Weight

The implementation of the Nagoya Protocol highlighted the importance of identifying alternative herbal products that are as effective as traditional medicine. Dipsacus asperoides and Phlomis umbrosa, two species used in the Korean medicine ‘Sok-dan’, are used for the treatment of bone- and arthritis-related diseases, and they are often mixed or misused. To identify herbal resources with similar efficacy, we compared the effects of D. asperoides extract (DAE) and P. umbrosa extract (PUE) on osteoarthritis (OA) in a monosodium iodoacetate (MIA)-induced OA rat model. Weight-bearing distribution, serum cytokines, histopathological features, and the expression of matrix metalloproteinases (MMPs) of knee joint tissues were examined in the OA rats treated with DAE and PUE (200 mg/kg) for 21 days. DAE and PUE restored weight-bearing distribution, inhibited the production of serum cytokines, and alleviated the histopathological features of the OA knee tissue. DAE or PUE treatment decreased OA-induced overexpression of MMP-2, MMP-9, and MMP-13 in the knee joint tissue. This study demonstrated the efficacy of both DAE and PUE in an MIA-induced OA model, providing a basis for the clinical use of these products in traditional Korean medicine.

Continuous Passive Motion and Loading System Design for the Study of Pro- and Anti-Inflamatory Mediators in Articular Cartilage

2009 ◽  
Author(s):  
Xiang Gu ◽  
Daniel Leong ◽  
Rashal Mahammud ◽  
Yong Hui Li ◽  
Hui Bin Sun ◽  
...  
Keyword(s):  
Articular Cartilage ◽  
Inflammatory Response ◽  
Knee Joint ◽  
Angular Displacement ◽  
Weight Bearing ◽  
Small Animal ◽  
Continuous Passive Motion ◽  
Mechanical Stimuli ◽  
Passive Motion

Joint diseases are common causes of disability worldwide. Physical activity and weight bearing conditions play an important role in the regulation of joint homeostasis throughout life. The parametric characterization of deleterious and beneficial joint loading regimens influencing the homeostasis of articular cartilage is of great interest from both a basic research and clinical practice point of view. The development of in vivo animal models is critical to investigate the underlying mechanisms mediating the biological response of articular joints to external mechanical stimuli. For this purpose, the design of a device capable of accurately control the joint motion and loading in a small animal is needed. In the present work, an assisted motion system was conceived to perform continuous passive motion (CPM) and continuous loaded motion (CLM) on the knee joint of a small animal in vivo. A major purpose of this system is the study of the inflammatory and anti-inflammatory response of cartilage under several biomechanical environments. Therefore, a key design criterion was to avoid any invasive intervention (i.e. intraskeletal fixators) that may produce an intrinsic inflammatory response and then obscure/mislead the assessment of the biological markers of interest. Other important design criteria include real time control of the knee joint position, angular displacement, cyclic motion frequency and custom load magnitude applied in the axial direction along the tibia.

LncRNA NEAT1 promotes inflammatory response and induces corneal neovascularization

2018 ◽  
Vol 61 (4) ◽  
pp. 231-239 ◽  
Author(s):  
Yan-hui Bai ◽  
Yong Lv ◽  
Wei-qun Wang ◽  
Guang-li Sun ◽  
Hao-hao Zhang
Keyword(s):  
Inflammatory Response ◽  
Rat Model ◽  
Noncoding Rna ◽  
Corneal Neovascularization ◽  
Inflammatory Factors ◽  
Enzyme Linked Immunosorbent Assay ◽  
Control Group ◽  
Protein Levels ◽  
Lncrna Neat1

Human corneal fibroblasts (HCFs) are implicated in corneal neovascularization (CRNV). The mechanisms underlying the inflammatory response in HCFs and the development of CRNV were explored in this study. Alkali burns were applied to the corneas of rats to establish a CRNV model. The expression of long noncoding RNA (lncRNA) nuclear enriched abundant transcript 1 (NEAT1) and mRNA and protein levels of nuclear factor kappa B (NF-κB)- activating protein (NKAP) were examined by quantitative real-time (qRT-PCR) and Western blot methods, respectively. Lipopolysaccharide (LPS) is used to stimulate HCFs for inflammatory response. The level of inflammation factors in HCF supernatant was detected using an enzyme-linked immunosorbent assay (ELISA). Binding and interactions between NEAT1 and miRNA 1246 (miR-1246) were determined by RNA immunoprecipitation (RIP) and RNA pull-down assays in HCFs. Compared with the control group (n = 6), NEAT1 was upregulated in the corneas of the CRNV rat model (n = 6). The expression of NEAT1 in HCFs was upregulated by LPS. Downregulation of NEAT1 suppressed the secretion of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6). NEAT1 could bind and interact with miR-1246. LPS regulated the expression of NKAP and NF-κB signaling via the NEAT1/miR-1246 pathway. Downregulation of NEAT1in vivoinhibited CRNV progression in the CRNV rat model. The lncRNA NEAT1 induced secretion of inflammatory factors, mediated by NF-κB, by targeting miR-1246, thereby promoting CRNV progression.

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