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 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 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 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.

scholarly journals Chondroprotective Effects and Multitarget Mechanisms of Fu Yuan Capsule in a Rat Osteoarthritis Model

2017 ◽  
Vol 2017 ◽  
pp. 1-11 ◽  
Author(s):  
Li Zeng ◽  
Cai Zhi Xiao ◽  
Zi Ting Deng ◽  
Rong Heng Li
Keyword(s):  
Articular Cartilage ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Cruciate Ligament ◽  
Interleukin 1 ◽  
Type Ii Collagen ◽  
Pharmacological Mechanism ◽  
Articular Cartilage Injury ◽  
Anterior Cruciate ◽  
A Disintegrin And Metalloproteinase

Fu Yuan Capsule (FYC) has been clinically used for osteoarthritis (OA) and its related diseases for many years in China. However, its pharmacological mechanism remains unclear. This study aimed to investigate the potential chondroprotective effects of FYC on articular cartilage. Rat OA model was induced by anterior cruciate ligament transection. A group of rats was treated with FYC for 12 weeks. Joint structure, types I and II collagen, and proteoglycan were evaluated by histological examination. The expression of C-terminal crosslinking telopeptide of type II collagen, hydroxyproline, a disintegrin and metalloproteinase with thrombospondin motifs, matrix metalloproteinase, interleukin-1 beta, nitric oxide, prostaglandin E2, heat-shock protein 70, transforming growth factor-beta, osteoprotegerin, and receptor activator of nuclear factor κB ligand were detected. Treatment with FYC could protect against articular cartilage injury. FYC treatment significantly decreased the extracellular matrix degradation factors and inflammatory mediators. Moreover, articular cartilage protective factors were increased in the FYC group. The current finding suggests that FYC protects articular cartilage in a rat OA model through various ways. Thus, it may be an effective agent for OA treatment.

scholarly journals Time-dependent gene expression and immunohistochemical analysis of the injured anterior cruciate ligament

2012 ◽  
Vol 1 (10) ◽  
pp. 238-244 ◽  
Author(s):  
T. Naraoka ◽  
Y. Ishibashi ◽  
E. Tsuda ◽  
Y. Yamamoto ◽  
T. Kusumi ◽  
...  
Keyword(s):  
Gene Expression ◽  
Anterior Cruciate Ligament ◽  
Cruciate Ligament ◽  
Immunohistochemical Analysis ◽  
Time Dependent ◽  
Anterior Cruciate
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