scholarly journals Expression of VEGF-A Signaling Pathway in Cartilage of ACLT-Induced Osteoarthritis Mouse Model

2021 ◽  
Author(s):  
Jiajia Qian ◽  
Qi Xu ◽  
Wei-min Xu ◽  
Ren Cai ◽  
Gui-cheng Huang
Keyword(s):  
Signaling Pathway ◽  
Cruciate Ligament ◽  
Underlying Mechanism ◽  
Clear Understanding ◽  
The Matrix ◽  
Cox 2 ◽  
Anterior Cruciate ◽  
A Disintegrin And Metalloproteinase ◽  
Safranin O ◽  
Endothelial Growth Factor

Abstract Background: The clear understanding of the underlying mechanism of Osteoarthritis(OA) remains elusive.Researches have shown that Vascular Endothelial Growth Factor(VEGF) induced angiogenesis and inflammation were important processes in the pathophysiology of OA.Now, Anterior Cruciate Ligament Transection surgery(ACLT) induced OA model was often used to invesgate the molecular mechanism of OA,but till now the angiogenesis and inflammation reaction in different pathological stages of ACLT-induced OA model has never been revealed.Methods:Moderate OA model was established by ACLT,and 1,2,4,8 and 12 weeks after surgery, Hematoxylin–eosin(HE) and Safranin-O(S-O) staining were used to detect the pathological changes in mouse knee cartilage,and the matrix biomarkers A Disintegrin and Metalloproteinase with Thrombospondin Motifs 5(ADAMTS5), Collagen II(COL-II) were detected using Immunohistochemistry (IHC),CD31 was detected by Immunofluorescence(IF) to show the vascular invasion in cartilage,and proteins expression of VEGF-A pathway were detected by Western blot(WB).Meanwhile the inflammatory biomarkers Cyclooxygenase-2 (COX-2) and inducible Nitric Oxide Synthase(Inos) in cartilage were detected by WB.Results:ACLT surgery can lead to degeneration of cartilage in mice,and the characteristics of the lesion were time dependent.The ADAMTS5 positive cells increased while COL-II decreased in OA cartilage with time,new blood vessel labeled by CD31 can been seen from 1 week in OA cartilage,and increased in 8 and 12 weeks.The expression of VEGF-A,VEGFR2,COX-2 and iNOS were higher than control groups,which were basically consistent with the degree of osteoarthritis.Conclusions:VEGF-A related signaling pathway played an irreplaceable role in the occurrence and development of ACLT model,and the underlying mechanism may be related to the angiogenesis and inflammation in cartilage.

scholarly journals Expression of VEGF-A Signaling Pathway in Cartilage of ACLT-induced Osteoarthritis Mouse Model

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Jia-jia Qian ◽  
Qi Xu ◽  
Wei-min Xu ◽  
Ren Cai ◽  
Gui-cheng Huang
Keyword(s):  
Signaling Pathway ◽  
Cruciate Ligament ◽  
Time Dependent ◽  
Pathological Changes ◽  
The Matrix ◽  
Vegfr2 Signaling ◽  
Cox 2 ◽  
Anterior Cruciate ◽  
A Disintegrin And Metalloproteinase ◽  
Safranin O

Abstract Background Anterior cruciate ligament transection surgery (ACLT)-induced OA model was often used to investigate the molecular mechanism of knee osteoarthritis (KOA). Researches have shown that vascular endothelial growth factor (VEGF) played an important role in OA. The present study aimed to investigate the pathological changes after ACLT surgery and reveal the expression characteristics of the VEGF-A/VEGFR2 signaling pathway in this model. Methods Moderate KOA model was established by ACLT, and 1, 2, 4, 8, and 12 weeks after surgery, hematoxylin-eosin (HE) and Safranin-O(S-O) staining were used to detect the pathological changes in mouse knee cartilage, and the matrix biomarkers A Disintegrin and Metalloproteinase with Thrombospondin Motifs 5(ADAMTS5), Collagen II (COL-II) were detected using immunohistochemistry (IHC), CD31 was detected by immunofluorescence (IF) to show the vascular invasion in cartilage, and proteins expression of VEGF-A pathway were detected by Western blot (WB). Meanwhile, the inflammatory biomarkers cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) in cartilage were detected by WB. Results ACLT surgery can lead to degeneration of cartilage in mice, and the characteristics of the lesion were time-dependent. The ADAMTS5-positive cells increased while COL-II decreased in OA cartilage with time, and new blood vessels labeled by CD31 can be seen from 1 week in OA cartilage, and increased in 8 and 12 weeks. The expression of VEGF-A, VEGFR2, COX-2, and iNOS were higher than control groups, which were basically consistent with the degree of osteoarthritis. Conclusions The degenerative degree of articular cartilage was time-dependent; angiogenesis and inflammation were important pathological changes of cartilage in KOA. The expression of the VEGF-A/VEGFR2 signaling pathway was basically correlated with the degree of KOA.

scholarly journals Treadmill Exercise after Controlled Abnormal Joint Movement Inhibits Cartilage Degeneration and Synovitis

Life ◽  
2021 ◽  
Vol 11 (4) ◽  
pp. 303
Author(s):  
Yuichiro Oka ◽  
Kenij Murata ◽  
Kaichi Ozone ◽  
Takuma Kano ◽  
Yuki Minegishi ◽  
...  
Keyword(s):  
Treadmill Exercise ◽  
Cruciate Ligament ◽  
Cartilage Degeneration ◽  
Research Society ◽  
Therapeutic Effects ◽  
Joint Movement ◽  
Knee Oa ◽  
Anterior Cruciate ◽  
Safranin O ◽  
Walking Group

Cartilage degeneration is the main pathological component of knee osteoarthritis (OA), but no effective treatment for its control exists. Although exercise can inhibit OA, the abnormal joint movement with knee OA must be managed to perform exercise. Our aims were to determine how controlling abnormal joint movement and treadmill exercise can suppress cartilage degeneration, to analyze the tissues surrounding articular cartilage, and to clarify the effect of treatment. Twelve-week-old ICR mice (n = 24) underwent anterior cruciate ligament transection (ACL-T) surgery on their right knees and were divided into three groups as follows: ACL-T, animals in the walking group subjected to ACL-T; controlled abnormal joint movement (CAJM), and CAJM with exercise (CAJM + Ex) (n = 8/group). Walking-group animals were subjected to treadmill exercise 6 weeks after surgery, including walking for 18 m/min, 30 min/day, 3 days/week for 8 weeks. Safranin-O staining, hematoxylin-eosin staining, and immunohistochemical staining were performed. The OARSI (Osteoarthritis research Society international) score was lower in the CAJM group than in the ACL-T group and was even lower in the CAJM + Ex group. The CAJM group had a lower meniscal injury score than the ACL-T group, and the CAJM + Ex group demonstrated a less severe synovitis than the ACL-T and CAJM groups. The observed difference in the perichondrium tissue damage score depending on the intervention method suggests different therapeutic effects, that normalizing joint motion can solve local problems in the knee joint, and that the anti-inflammatory effect of treadmill exercise can suppress cartilage degeneration.

scholarly journals Extract of the Blood Circulation-Promoting Recipe-84 Can Protect Rat Retinas by Inhibiting the β-Catenin Signaling Pathway

2018 ◽  
Vol 19 (9) ◽  
pp. 2712 ◽  
Author(s):  
Qiu-Fang Qin ◽  
Min Liu ◽  
Gui-Hua Tian ◽  
Jian Chen ◽  
Yu-Sang Li
Keyword(s):  
Ganglion Cell ◽  
Signaling Pathway ◽  
Retinal Ganglion Cell ◽  
Blood Circulation ◽  
Dependent Manner ◽  
Retinal Ganglion ◽  
Expression Levels ◽  
Cox 2 ◽  
Endothelial Growth Factor

Extract of the Blood Circulation-Promoting Recipe (EBR-84) from the Chinese Herbal medicine “Blood Circulation Promoting Recipe” could retard retinopathy development. This study investigated whether EBR-84 protects retinas by inhibiting the β-catenin pathway using a rat model of retinopathy and a retinal ganglion cell 5 (RGC-5) cell death model. RGC death was induced by either N-methyl-d-aspartic acid (NMDA) or TWS119 (an activator of the β-catenin pathway). After the corresponding treatment with EBR-84, RGC death and the protein expression levels of β-catenin, cyclooxygenase-2 (COX-2), and vascular endothelial growth factor (VEGF) in rat retinas were examined. β-Catenin accumulated in the retinal ganglion cell layer (GCL) of NMDA-treated rats. EBR-84 (3.9, 7.8, and 15.6 g/kg) significantly attenuated the NMDA-induced RGC loss accompanying the reduction of β-catenin expression. Moreover, the expression levels of COX-2 and VEGF were decreased by EBR-84 in a dose-dependent manner. For the TWS119-treated rats, EBR-84 also ameliorated RGC loss and lowered the expression levels of β-catenin, COX-2, and VEGF. In vitro, EBR-84 increased the viability of NMDA-treated RGC-5 while decreased β-catenin expression. In conclusion, EBR-84 retarded ratretinopathy, and the β-catenin signaling pathway played an important role during this protective process.

scholarly journals The underlying mechanism of partial anterior cruciate ligament injuries to the meniscus degeneration of knee joint in rabbit models

2020 ◽  
Author(s):  
Dalin Wang ◽  
Zhe Wang ◽  
Mingcheng Li ◽  
Songbao Xu
Keyword(s):  
Anterior Cruciate Ligament ◽  
Knee Joint ◽  
Cruciate Ligament ◽  
Underlying Mechanism ◽  
Joint Fluid ◽  
Control Group ◽  
Rabbit Knee ◽  
Meniscus Degeneration ◽  
Anterior Cruciate ◽  
Experimental Group

Abstract Background: The diagnosis, treatment and efficacy evaluation of anterior cruciate ligament (ACL) partial rupture remains controversial. This research aims to investigate the underlying mechanism of partial ACL injuries to the meniscus degeneration in the rabbit knee.Methods: Sixty New Zealand, white rabbits were randomly divided into three groups including an experimental group, a sham group (n=6) and and a blank control group (n=6). The experimental group is composed of an anteromedial bundle (AMB) rupture group (n=24), a posterolateral bundle (PLB) rupture group (n=24). Rabbits in the experimental group were subjected to right hind limbs knee surgery to induce ACL part injury under the arthroscopy. Finally, eight rabbits including 6 in the model group and 2 in the control group were sampled randomly on the second, fourth and eighth weeks respectively. We observed the typical form of the meniscus through HE staining. Expressions of inflammatory factors including interleukin-1β (IL-1β) and IL-17 in the knee joint fluid were determined by means of an ELISA. Analysis of the mRNA expressions of matrix metalloproteinases-13(MMP-13) was performed to evaluate the inflammatory mediators in the pathogenesis of the meniscus.Results: HE staining results showed that the surface was rough and the tissues were loose displaying collagen fibers of varying thickness. Both IL-1β and IL-17 in the synovial fluid, and the positive rate of MMP-13 in addition to MMP-13 mRNA showed a demonstrable increase treads from the 2nd to the 8th week. The significant difference was found (P<0.05) compared to the control group.Conclusion: We conclude that the elevated levels of IL-1β and IL-17, along with increased MMP13 expression, resulted in meniscus degradation in the rabbit knee joint model with partial ACL injury.

scholarly journals Acupuncture reduces pain in rats with osteoarthritis by inhibiting MCP2/CCR2 signaling pathway

2020 ◽  
Vol 245 (18) ◽  
pp. 1722-1731
Author(s):  
Bocun Li ◽  
Li Jing ◽  
Li Jia ◽  
Tan Qian ◽  
Chen Jianyi ◽  
...  
Keyword(s):  
Protective Effect ◽  
Cruciate Ligament ◽  
Alternative Therapy ◽  
Cartilage Degeneration ◽  
Underlying Mechanism ◽  
Sprague Dawley ◽  
Nerve Sprouting ◽  
Anterior Cruciate ◽  
The Right ◽  
And Cartilage

Acupuncture is an emerging alternative therapy that has been beneficial for the pain of osteoarthritis (OA). However, the underlying mechanism of protective effect remains unclear. MCP1/CCR2 axis can be stimulated in various periods of OA, and we hypothesize that acupuncture may treat OA by regulating the MCP1/CCR2 axis. This study aimed to explore the effect of acupuncture at points ST35 and ST36 on the effects of hyperalgesia and cartilage in OA rats including the expression of chemokines, nerve growth factor (NGF), and inflammatory-related proteins. OA was induced in male Sprague–Dawley rats by anterior cruciate ligament transection at the right knee. The first acupuncture intervention was performed on the seventh day after surgery and once a day for seven weeks. The knee-pain-related behaviors, histology, and related protein were examined in this study. We have found that electroacupuncture at ST35 and ST36 can significantly alleviate the hyperalgesia and cartilage degeneration as well as reducing nerve sprouting in OA knee joint. Moreover, acupuncture treatment may inhibit the MCP1/CCR2 axis as well as down-regulate inflaming factor and NGF in cartilage and synovial tissue. The data presented here indicate that acupuncture exerts a protective effect against hyperalgesia and cartilage degeneration, and the mechanism might involve in chemokines and NGF pathway.

scholarly journals Impact of Controlling Abnormal Joint Movement on the Effectiveness of Subsequent Exercise Intervention in Mouse Models of Early Knee Osteoarthritis

Cartilage ◽  
2019 ◽  
pp. 194760351988500
Author(s):  
Yuichiro Oka ◽  
Kenji Murata ◽  
Takuma Kano ◽  
Kaichi Ozone ◽  
Kohei Arakawa ◽  
...  
Keyword(s):  
Mechanical Stress ◽  
Exercise Intervention ◽  
Cruciate Ligament ◽  
Cartilage Degeneration ◽  
Research Society ◽  
Joint Movement ◽  
Knee Oa ◽  
Osteoarthritis Research Society ◽  
Anterior Cruciate ◽  
Safranin O

Objective Moderate mechanical stress is necessary for preserving the cartilage. The clinician empirically understands that prescribing only exercise will progress osteoarthritis (OA) for knee OA patients with abnormal joint movement. When prescribing exercise for OA, we hypothesized that degeneration of articular cartilage could be further prevented by combining interventions with the viewpoint of normalizing joint movement. Design Twelve-week-old ICR mice underwent anterior cruciate ligament transection (ACL-T) surgery in their right knee and divided into 4 groups: ACL-T, controlled abnormal joint movement (CAJM), ACL-T with exercise (ACL-T/Ex), CAJM with exercise (CAJM/Ex). Animals in the walking group were subjected to treadmill exercise 6 weeks after surgery, which included walking for 18 m/min, 30 min/d, 3 d/wk for 4 weeks. Joint instability was measured by anterior drawer test, and safranin-O staining and immunohistochemical staining were performed. Results OARSI (Osteoarthritis Research Society International) score of ACL-T/Ex group showed highest among 4 groups ( P < 0.001). And CAJM/Ex group was lower than ACL-T/Ex group. Positive cell ratio of IL-1β and MMP-13 in CAJM/Ex group was lower than ACL-T/Ex group ( P < 0.05). Conclusions We found that the state of the intra-articular environment can greatly influence the effect of exercise on cartilage degeneration, even if exercise is performed under the same conditions. In the CAJM/Ex group where joint movement was normalized, abnormal mechanical stress such as shear force and compression force accompanying ACL cutting was alleviated. These findings may highlight the need to consider an intervention to correct abnormal joint movement before prescribing physical exercise in the treatment of OA.

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