The Experts below are selected from a list of 360 Experts worldwide ranked by ideXlab platform
Kun Wang - One of the best experts on this subject based on the ideXlab platform.
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curcumin inhibits Joint Contracture through pten demethylation and targeting pi3k akt mtor pathway in myofibroblasts from human Joint capsule
Evidence-based Complementary and Alternative Medicine, 2019Co-Authors: Ze Zhuang, Zheng Chen, Dezhao Liu, Guohui Yuan, Linlin Sun, Yuangao Liu, Ni Yirong, Kun WangAbstract:Joint Contracture is increasingly regarded as a clinical problem that leads to irreversible dysfunction of the Joint. It is a pathophysiological process following Joint injury, which is marked by the activation of myofibroblasts. There is currently no effective treatment for the prevention of Joint Contracture. Curcumin is a polyphenol pigment extracted from turmeric, which possesses anti-inflammatory, antioxidative, and antitumor properties. In the present study, we demonstrated that curcumin exerts a protective effect against Joint Contracture via the inhibition of myofibroblast proliferation and migration in a time- and concentration-dependent manner. Moreover, we indicated that phosphatase and tension homolog (PTEN) was downregulated in myofibroblasts in vitro and in the Contracture capsule tissues of patients in vivo. Additionally, western blot analysis revealed a negative correlation between the expression levels of PTEN and the fibrosis marker protein alpha smooth muscle cell actin. Methylation-specific PCR results suggested that curcumin was able to demethylate PTEN in a similar manner to the demethylation agent 5-azacytidine, increasing PTEN expression and further inhibiting phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin signaling. In conclusion, our data illustrate part of the mechanism of curcumin inhibition in Joint Contracture. These results support the hypothesis that curcumin may potentially be used as a novel candidate for the treatment of Joint Contracture.
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a mini invasive internal fixation technique for studying immobilization induced knee flexion Contracture in rats
Journal of Visualized Experiments, 2019Co-Authors: Shihai Jiang, Yuangao Liu, Lei Zhu, Yuansen Luo, Fei Zhang, Kun WangAbstract:Joint Contracture, resulting from a prolonged Joint immobilization, is a common complication in orthopedics. Currently, utilizing an internal fixation to restrict knee Joint mobility is a widely accepted model to generate experimental Contracture. However, implanting application will inevitably cause surgical trauma to the animals. Aiming to develop a less invasive approach, we combined a muscle-gap separation modus with a previously reported mini-incision skill during the surgical procedure: Two mini skin incisions were made on the lateral thigh and leg, followed by performing muscle-gap separation to expose the bone surface. The rat knee Joint was gradually immobilized by a preconstructed internal fixation at approximately 135° knee flexion without interfering essential nerves or blood vessels. As expected, this simple technique permits rapid postoperative rehabilitation in animals. The correct position of the internal fixation was confirmed by an x-ray or micro-CT scanning analysis. The range of motion was significantly restricted in the immobilized knee Joint than that observed in the contralateral knee Joint demonstrating the effectiveness of this model. Besides, histological analysis revealed the development of fibrous deposition and adhesion in the posterior-superior knee Joint capsule over time. Thus, this mini-invasive model may be suitable for mimicking the development of immobilized knee Joint Contracture.
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overexpression of chaperonin containing t complex polypeptide subunit zeta 2 cct6b suppresses the functions of active fibroblasts in a rat model of Joint Contracture
Journal of Orthopaedic Surgery and Research, 2019Co-Authors: Zhe Wang, Ze Zhuang, Jianhua Ren, Kaihua Liu, Kun WangAbstract:Background Joint Contracture is a fibrous disease characterized as Joint capsule fibrosis that results in Joint dysfunction and disability. The purpose of this study was to analyze the biological activities of chaperonin containing T-complex polypeptide (CCT) subunits and to determine the role of CCT chaperone in Joint Contracture in a rat model.
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Overexpression of chaperonin containing T-complex polypeptide subunit zeta 2 (CCT6b) suppresses the functions of active fibroblasts in a rat model of Joint Contracture
Journal of orthopaedic surgery and research, 2019Co-Authors: Zhe Wang, Ze Zhuang, Jianhua Ren, Kaihua Liu, Kun WangAbstract:Joint Contracture is a fibrous disease characterized as Joint capsule fibrosis that results in Joint dysfunction and disability. The purpose of this study was to analyze the biological activities of chaperonin containing T-complex polypeptide (CCT) subunits and to determine the role of CCT chaperone in Joint Contracture in a rat model. In this study, the rat model of Joint Contracture was established by immobilizing the rat knee for 8 weeks. Then, fibroblasts were isolated from the posterior Joint capsule and were cultured for functional analysis such as qRT-PCR, Western blot, transwell assay, and collagen assay. The effect of CCT subunit was determined by employing a lentivirus containing target gene and transfecting it into fibroblasts. Results of qRT-PCR and Western blot showed that among all CCT subunits, CCT6b significantly decreased in the fibroblasts from contractive Joints compared to cells from normal Joints (p < 0.05). Overexpression of CCT6b by transfection of lentivirus containing CCT6b gene to active fibroblasts significantly inhibited fibrous marker (α-SMA, COL-1) expressions, fibroblast migration, and collagen synthesis (all p < 0.05). Moreover, fibrosis-related chaperone CCT7 expression was decreased with CCT6b overexpression (p < 0.05). The biological activities of CCT subunits in fibroblasts from the Joint Contracture rat model were analyzed in this study. CCT6b significantly decreased in the active fibroblasts, and overexpression of CCT6b significantly inhibited fibroblast functions. These findings indicate that CCT6b appears to be a potential molecular biomarker and therapeutic target for the novel therapies of Joint Contracture.
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Endoplasmic reticulum stress-dependent ROS production mediates synovial myofibroblastic differentiation in the immobilization-induced rat knee Joint Contracture model.
Experimental cell research, 2018Co-Authors: Shihai Jiang, Zhe Wang, Jianhua Ren, Lei Zhu, Tangzhao Liang, Dahai Xiao, Kun WangAbstract:Abstract Joint Contracture is a common complication for people with Joint immobility that involves fibrosis structural alteration in the Joint capsule. Considering that endoplasmic reticulum (ER) stress plays a prominent role in the promotion of tissue fibrosis, we investigated whether the unfolded protein response (UPR) contributes to the fibrotic development in immobilization-induced knee Joint Contractures. Using a non-traumatic rat knee Joint Contracture model, twelve female Sprague-Dawley rats received knee Joint immobilization for a period of 8 weeks. We found that fibrosis protein markers (type I collagen, α-SMA) and UPR (GRP78, ATF6α, XBP1s) markers were parallelly upregulated in rat primary cultured synovial myofibroblasts. In the same cell types, pre-treatment with an ER stress inhibitor, 4-phenylbutyric acid (4-PBA), not only abrogated cytokine TGFβ1 stimulation but also reduced the protein level of UPR. Additionally, high reactive oxygen species (ROS) generation was detected in synovial myofibroblasts through flow cytometry, as expected. Notably, TGFβ1-induced UPR was significantly reduced through the inhibition of ROS with antioxidants. These data suggest that ER stress act as a pro-fibrotic stimulus through the overexpression of ROS in synovial fibroblasts. Interestingly, immunohistochemical results showed an increase in the UPR protein levels both in human acquired Joint Contractures capsule tissue and in animal knee Joint Contracture tissue. Together, our findings suggest that ER stress contributes to synovial myofibroblastic differentiation in Joint capsule fibrosis and may also serve as a potential therapeutic target in Joint Contractures.
Joaquin Sanchezsotelo - One of the best experts on this subject based on the ideXlab platform.
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intra articular injection of a substance p inhibitor affects gene expression in a Joint Contracture model
Journal of Cellular Biochemistry, 2018Co-Authors: Mark E. Morrey, Eric A. Lewallen, Diane E. Grill, Scott P. Steinmann, Jie J. Yao, Christopher G. Salib, William H. Trousdale, Nicolas Reina, Joaquin Sanchezsotelo, Hilal Maradit KremersAbstract:Substance P (SP), a neurotransmitter released after injury, has been linked to deregulated tissue repair and fibrosis in musculoskeletal tissues and other organs. Although SP inhibition is an effective treatment for nausea, it has not been previously considered as an anti-fibrotic therapy. Although there are extensive medical records of individuals who have used SP antagonists, our analysis of human registry data revealed that patients receiving these antagonists and arthroplasty are exceedingly rare, thus precluding a clinical evaluation of their potential effects in the context of arthrofibrosis. Therefore, we pursued in vivo studies to assess the effect of SP inhibition early after injury on pro-fibrotic gene expression and Contractures in an animal model of post-traumatic Joint stiffening. Skeletally mature rabbits (n = 24) underwent surgically induced severe Joint Contracture, while injected with either fosaprepitant (a selective SP antagonist) or saline (control) early after surgery (3, 6, 12, and 24 hours). Biomechanical testing revealed that differences in mean Contracture angles between the groups were not statistically significant (p = 0.27), suggesting that the drug neither mitigates nor exacerbates Joint Contracture. However, microarray gene expression analysis revealed that mRNA levels for proteins related to cell signaling, pro-angiogenic, pro-inflammatory and collagen matrix production were significantly different between control and fosaprepitant treated rabbits (p < 0.05). Hence, our study demonstrates that inhibition of SP alters expression of pro-fibrotic genes in vivo. This finding will motivate future studies to optimize interventions that target SP to reduce the formation of post-traumatic Joint Contractures. This article is protected by copyright. All rights reserved
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molecular landscape of arthrofibrosis microarray and bioinformatic analysis of the temporal expression of 380 genes during Contracture genesis
Gene, 2017Co-Authors: Mark E. Morrey, Matthew P Abdel, Bernard F Morrey, Amel Dudakovic, Andre J. Van Wijnen, Scott M Riester, Joaquin SanchezsoteloAbstract:Abstract Purpose Inflammatory changes are suspected in the pathophysiology of arthrofibrosis formation and require early molecular examination. Here, we assessed the hypothesis that early inflammatory genes are related to arthrofibrosis by ascertaining gene expression during the early stages of Contracture genesis in an animal model. Methods Joint trauma was incited surgically in a cohort of rabbits (n = 36) knees followed by immobilization in a model of Contracture. Six groups of 6 rabbits were sacrificed at multiple time points (0, 6, 12, 24, 72 h and 2 weeks). Microarray expression and RT-qPCR profiling were performed to determine genes that are significantly up or downregulated. Bioinformatic analysis was carried out to understand which biological programs and functional groups of genes are modulated in arthrofibrosis. Results Gene expression profiling revealed a large number biologically relevant genes (> 100) that are either upregulated or downregulated by at least a 1.5 fold (log2) during the first two weeks after Joint injury during Contracture development. Gene ontology analysis identified molecular pathways and programs that act during the course of fibrosis and Joint Contracture. Our main finding is that the development of Contractures occur concomitant with modulation of genes mediating inflammatory responses, ECM remodeling and the epithelial-to-mesenchymal transition. Conclusion The genesis of Joint Contracture reflects an imbalance between pro- and anti-fibrotic expression. Our study indicates that inflammatory genes may be involved in the process of Contracture genesis and initiated at relatively early stages. Our findings also may inform clinical practice in the future by suggesting potential therapeutic targets in preventing the long-term development of arthrofibrosis.
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surgical capsular release reduces flexion Contracture in a rabbit model of arthrofibrosis
Journal of Orthopaedic Research, 2013Co-Authors: Jonathan D Barlow, Mark E. Morrey, Scott P. Steinmann, Matthew P Abdel, Bernard F Morrey, Robert U Hartzler, Joaquin SanchezsoteloAbstract:Animal models of Joint Contracture may be used to elucidate the mechanisms of arthrofibrosis. Patients with Joint Contracture commonly undergo surgical capsular release. Previous animal models of Joint Contracture do not simulate this aspect of arthrofibrosis. We hypothesize that a surgical capsular release will decrease the severity of arthrofibrosis in this rabbit model. A capsular Contracture was surgically created in 20 skeletally mature rabbits. Eight weeks later, ten rabbits underwent capsular release, which consisted of elevation of the posterior capsule through a lateral incision and manipulation under anesthesia. Ten rabbits had a sham incision, without release (control group). Immediately after release or sham surgery, extension loss (calculated by subtracting the knee extension angle (degrees) of the operative limb from the nonoperative, contralateral limb) was measured using fluoroscopy. All animals were sacrificed following 16 weeks of postoperative free cage activity. At sacrifice, Joint Contracture was measured using a custom, calibrated device. The histology of the posterior Joint capsule was assessed at sacrifice. All animals survived both operations without complications. Immediately after surgical release or sham surgery, the average extension loss was 129.2 ± 10.7° in the control group versus 29.6 ± 8.2° in the capsular release group (p = 0.0002). Following 16 weeks of remobilization, the average extension loss of the control and capsular release animals were 49.0 ± 12.7° and 36.5 ± 14.2°, respectively (p = 0.035). There were no histological differences between the two groups. In this animal model, a surgical capsular release decreased the extension loss (flexion Contracture) immediately after surgery, as well as following sixteen weeks of remobilization. There were no histological changes detected in the posterior Joint capsule. © 2013 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 31:1529–1532, 2013
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myofibroblast cells are preferentially expressed early in a rabbit model of Joint Contracture
Journal of Orthopaedic Research, 2012Co-Authors: Matthew P Abdel, Mark E. Morrey, Scott P. Steinmann, Jonathan D Barlow, Cole R Kreofsky, Bernard F Morrey, Joaquin SanchezsoteloAbstract:Studies have demonstrated increased myofibroblasts in Contractures. However, the timeline is largely unknown. The aim of this study was to determine the number of myofibroblasts in contracting Joint capsules at 3-time points over a 24-week period. Eighteen rabbits subjected to a surgical procedure designed to elicit a knee Joint Contracture were divided into three groups of six. Rabbits were sacrificed at each respective time point and myofibroblasts in the Joint capsules were quantified using immunohistochemistry. The percent of myofibroblasts was significantly elevated in the operated limbs compared to the control limbs at 2 weeks (20% vs. 7%, respectively; p = 0.014). There was no difference in the percent of myofibroblasts between the operated and control limbs at 8 or 24 weeks (p = 0.96 and 0.07, respectively). The percent of myofibroblasts dropped from 20% at 2 weeks to 3.0% at 8 weeks (p < 0.001). The decrease from 8 to 24 weeks was not significant (p = 0.19). A large proportion of myofibroblasts are present in contracted Joints at 2 weeks. By week 8, the proportion of myofibroblasts seem to return to normal. Interventions aimed at affecting the myofibroblast cell in order to prevent fibrosis should be instituted early. © 2011 Orthopaedic Research Society Published by Wiley Periodicals, Inc. J Orthop Res 30:713–719, 2012
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new rabbit knee model of posttraumatic Joint Contracture indirect capsular damage induces a severe Contracture
Journal of Orthopaedic Research, 2009Co-Authors: Sergiy Nesterenko, Mark E. Morrey, Scott P. Steinmann, Matthew P Abdel, Bernard F Morrey, Joaquin SanchezsoteloAbstract:Reported models of Joint Contracture fail to result in severe motion loss. Our purpose was to develop a rabbit model of knee Contracture and compare it to another well-accepted model to determine if more severe stiffness can be achieved. Sixteen skeletally mature New Zealand White female rabbits had their right knee operated to create 3-mm defects on the noncartilaginous portions of the femoral condyles, hyperextend the Joint to disrupt the posterior capsule, and immobilize the Joint in maximum flexion with a Kirschner-wire for 8 weeks (group I). Sixteen additional rabbits were operated on using an identical protocol except for the absence of capsular injury (group II). In each group, mechanical testing was performed at the time of Kirschner-wire release in eight animals, and 16 weeks after remobilization in eight animals. At immobilization release, the average Contracture was 76 +/- 24 degrees in group I versus 20 +/- 10 degrees in group II (p < 0.001). Sixteen weeks after remobilization, the mean Contracture was 49 +/- 15 degrees group I versus 11 +/- 10 degrees in group II (p < 0.001). When associated with bone perforations and immobilization in forced flexion, injury to the posterior capsule results in a severe Contracture in the rabbit knee.
Yi Liu - One of the best experts on this subject based on the ideXlab platform.
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effect of ultrashort wave treatment on Joint dysfunction and muscle atrophy in a rabbit model of extending knee Joint Contracture enhanced expression of myogenic differentiation
Knee, 2020Co-Authors: Feng Wang, Quan-bing Zhang, Yun Zhou, Peng-peng Huang, Ying A Liu, Yi LiuAbstract:Abstract Objective To investigate the effects of ultrashort wave treatment on Joint dysfunction and muscle atrophy in a rabbit model of extending knee Joint Contracture. Methods Forty rabbits were randomly divided into eight groups. In group C, the left knee Joint was not fixed. In group I-8, the left knee Joint was only fixed for eight weeks. In groups R-1, R-2, and R-4, the left knee Joint was fixed for eight weeks before the rabbits underwent one, two, and four weeks of self-recovery, respectively. In groups T-1, T-2, and T-4, the left knee Joint was fixed for eight weeks before the rabbits underwent one, two, and four weeks of ultrashort wave treatment, respectively. The degree of total Contracture and myogenic Contracture were measured, the cross-sectional area (CSA) and protein levels for myogenic differentiation (MyoD) of the rectus femoris were evaluated. Results There was a tendency toward a reduced degree of total and myogenic Contracture, and also a tendency toward an increased CSA of the rectus femoris and increased protein levels for MyoD after both self-recovery and ultrashort wave treatment. The ultrashort wave was more effective than self-recovery in reducing the total and myogenic Contracture, and increasing the CSA and MyoD protein levels of the rectus femoris. Conclusions Ultrashort wave treatment may ameliorate Joint dysfunction and muscle atrophy by upregulating the expression of MyoD protein in a rabbit model of extending knee Joint Contracture.
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The mechanisms and treatments of muscular pathological changes in immobilization-induced Joint Contracture: A literature review.
Chinese journal of traumatology = Zhonghua chuang shang za zhi, 2019Co-Authors: Feng Wang, Quan-bing Zhang, Yun Zhou, Shuang Chen, Peng-peng Huang, Yi LiuAbstract:The clinical treatment of Joint Contracture due to immobilization remains difficult. The pathological changes of muscle tissue caused by immobilization-induced Joint Contracture include disuse skeletal muscle atrophy and skeletal muscle tissue fibrosis. The proteolytic pathways involved in disuse muscle atrophy include the ubiquitin-proteasome-dependent pathway, caspase system pathway, matrix metalloproteinase pathway, Ca2+-dependent pathway and autophagy-lysosomal pathway. The important biological processes involved in skeletal muscle fibrosis include intermuscular connective tissue thickening caused by transforming growth factor-β1 and an anaerobic environment within the skeletal muscle leading to the induction of hypoxia-inducible factor-1α. This article reviews the progress made in understanding the pathological processes involved in immobilization-induced muscle Contracture and the currently available treatments. Understanding the mechanisms involved in immobilization-induced Contracture of muscle tissue should facilitate the development of more effective treatment measures for the different mechanisms in the future.
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The mechanisms and treatments of muscular pathological changes in immobilization-induced Joint Contracture: A literature review
Elsevier, 2019Co-Authors: Feng Wang, Quan-bing Zhang, Yun Zhou, Shuang Chen, Peng-peng Huang, Yi LiuAbstract:The clinical treatment of Joint Contracture due to immobilization remains difficult. The pathological changes of muscle tissue caused by immobilization-induced Joint Contracture include disuse skeletal muscle atrophy and skeletal muscle tissue fibrosis. The proteolytic pathways involved in disuse muscle atrophy include the ubiquitin-proteasome-dependent pathway, caspase system pathway, matrix metalloproteinase pathway, Ca2+-dependent pathway and autophagy-lysosomal pathway. The important biological processes involved in skeletal muscle fibrosis include intermuscular connective tissue thickening caused by transforming growth factor-β1 and an anaerobic environment within the skeletal muscle leading to the induction of hypoxia-inducible factor-1α. This article reviews the progress made in understanding the pathological processes involved in immobilization-induced muscle Contracture and the currently available treatments. Understanding the mechanisms involved in immobilization-induced Contracture of muscle tissue should facilitate the development of more effective treatment measures for the different mechanisms in the future. Keywords: Immobilization-induced Joint Contracture, Disuse skeletal muscle atrophy, Skeletal muscle fibrosis, Treatmen
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Rabbit Model of Extending Knee Joint Contracture: Progression of Joint Motion Restriction and Subsequent Joint Capsule Changes after Immobilization.
Journal of Knee Surgery, 2018Co-Authors: Yun Zhou, Quan-bing Zhang, Huazhang Zhong, Yi Liu, Jue Hua JingAbstract:This study aimed to develop a rabbit model of knee Contracture in extension and investigate the natural history of motion loss and time-dependent changes in the Joint capsule after immobilization. We immobilized the unilateral knee Joints of 32 rabbits by maintaining the knee Joint in a plaster cast at full extension. Eight rabbits were euthanized at 2, 4, 6, and 8 weeks after casting, respectively, and the lower extremities were disarticulated at the hip Joint. Eight control group rabbits that did not undergo immobilization were also examined. We assessed the progression of Joint Contracture by measuring the Joint range of motion, evaluating the histologic alteration of the capsule, and assessing the mRNA levels of transforming growth factor β1 (TGF-β1) in the anterior and posterior Joint capsules. After 2 weeks of Joint immobilization, the knee Joint range of motion was limited, the synovial membrane of the suprapatellar and posterior Joint capsules was thickened, the collagen deposition was increased, and the mRNA levels of TGF-β1 were elevated in the anterior and posterior Joint capsules. These changes progressed rapidly until 6 weeks of immobilization and may advance slowly after 6 weeks. Joint Contracture developed at the early stage of immobilization and progressed over time. The changes in the anterior and posterior Joint capsules after Joint immobilization may contribute to the limitation in flexion. The elevated mRNA expression of TGF-β1 may be related to Joint capsule fibrosis and may be one of the causes of Joint Contracture.
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effect of stretching combined with ultrashort wave diathermy on Joint function and its possible mechanism in a rabbit knee Contracture model
American Journal of Physical Medicine & Rehabilitation, 2017Co-Authors: Quan-bing Zhang, Yun Zhou, Huazhang Zhong, Yi LiuAbstract:Objective The aim of this study was to investigate the therapeutic effect of stretching combined with ultrashort wave on Joint Contracture and explore its possible mechanism. Design Thirty-two rabbits underwent unilateral immobilization of a knee Joint at full extension to cause Joint Contracture. At 6 wks after immobilization, the rabbits were randomly divided into the following four groups: natural recovery group, stretching treatment group, ultrashort wave treatment group, and combined treatment group. For comparison, eight control group animals of corresponding age were also examined. The effect of stretching and ultrashort wave treatment on Joint Contracture was assessed by measuring the Joint range of motion, evaluating the collagen deposition of Joint capsule and assessing the mRNA and protein levels for transforming growth factor β1 in the Joint capsule. Results The combined treatment group led to the best recovery of Joint function. The combined treatment with stretching and ultrashort wave was more effective than stretching or ultrashort wave treatment alone against the synovial thickening of suprapatellar Joint capsule, the collagen deposition of anterior Joint capsule, and the elevated expression of transforming growth factor β1 in the Joint capsule. Conclusions Stretching combined with ultrashort wave treatment was effective in improving Joint range of motion, reducing the biomechanical, histological, and molecular manifestations of Joint capsule fibrosis in a rabbit model of extending Joint Contracture.
Zhe Wang - One of the best experts on this subject based on the ideXlab platform.
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Overexpression of chaperonin containing T-complex polypeptide subunit zeta 2 (CCT6b) suppresses the functions of active fibroblasts in a rat model of Joint Contracture
Journal of orthopaedic surgery and research, 2019Co-Authors: Zhe Wang, Ze Zhuang, Jianhua Ren, Kaihua Liu, Kun WangAbstract:Joint Contracture is a fibrous disease characterized as Joint capsule fibrosis that results in Joint dysfunction and disability. The purpose of this study was to analyze the biological activities of chaperonin containing T-complex polypeptide (CCT) subunits and to determine the role of CCT chaperone in Joint Contracture in a rat model. In this study, the rat model of Joint Contracture was established by immobilizing the rat knee for 8 weeks. Then, fibroblasts were isolated from the posterior Joint capsule and were cultured for functional analysis such as qRT-PCR, Western blot, transwell assay, and collagen assay. The effect of CCT subunit was determined by employing a lentivirus containing target gene and transfecting it into fibroblasts. Results of qRT-PCR and Western blot showed that among all CCT subunits, CCT6b significantly decreased in the fibroblasts from contractive Joints compared to cells from normal Joints (p < 0.05). Overexpression of CCT6b by transfection of lentivirus containing CCT6b gene to active fibroblasts significantly inhibited fibrous marker (α-SMA, COL-1) expressions, fibroblast migration, and collagen synthesis (all p < 0.05). Moreover, fibrosis-related chaperone CCT7 expression was decreased with CCT6b overexpression (p < 0.05). The biological activities of CCT subunits in fibroblasts from the Joint Contracture rat model were analyzed in this study. CCT6b significantly decreased in the active fibroblasts, and overexpression of CCT6b significantly inhibited fibroblast functions. These findings indicate that CCT6b appears to be a potential molecular biomarker and therapeutic target for the novel therapies of Joint Contracture.
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overexpression of chaperonin containing t complex polypeptide subunit zeta 2 cct6b suppresses the functions of active fibroblasts in a rat model of Joint Contracture
Journal of Orthopaedic Surgery and Research, 2019Co-Authors: Zhe Wang, Ze Zhuang, Jianhua Ren, Kaihua Liu, Kun WangAbstract:Background Joint Contracture is a fibrous disease characterized as Joint capsule fibrosis that results in Joint dysfunction and disability. The purpose of this study was to analyze the biological activities of chaperonin containing T-complex polypeptide (CCT) subunits and to determine the role of CCT chaperone in Joint Contracture in a rat model.
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Endoplasmic reticulum stress-dependent ROS production mediates synovial myofibroblastic differentiation in the immobilization-induced rat knee Joint Contracture model.
Experimental cell research, 2018Co-Authors: Shihai Jiang, Zhe Wang, Jianhua Ren, Lei Zhu, Tangzhao Liang, Dahai Xiao, Kun WangAbstract:Abstract Joint Contracture is a common complication for people with Joint immobility that involves fibrosis structural alteration in the Joint capsule. Considering that endoplasmic reticulum (ER) stress plays a prominent role in the promotion of tissue fibrosis, we investigated whether the unfolded protein response (UPR) contributes to the fibrotic development in immobilization-induced knee Joint Contractures. Using a non-traumatic rat knee Joint Contracture model, twelve female Sprague-Dawley rats received knee Joint immobilization for a period of 8 weeks. We found that fibrosis protein markers (type I collagen, α-SMA) and UPR (GRP78, ATF6α, XBP1s) markers were parallelly upregulated in rat primary cultured synovial myofibroblasts. In the same cell types, pre-treatment with an ER stress inhibitor, 4-phenylbutyric acid (4-PBA), not only abrogated cytokine TGFβ1 stimulation but also reduced the protein level of UPR. Additionally, high reactive oxygen species (ROS) generation was detected in synovial myofibroblasts through flow cytometry, as expected. Notably, TGFβ1-induced UPR was significantly reduced through the inhibition of ROS with antioxidants. These data suggest that ER stress act as a pro-fibrotic stimulus through the overexpression of ROS in synovial fibroblasts. Interestingly, immunohistochemical results showed an increase in the UPR protein levels both in human acquired Joint Contractures capsule tissue and in animal knee Joint Contracture tissue. Together, our findings suggest that ER stress contributes to synovial myofibroblastic differentiation in Joint capsule fibrosis and may also serve as a potential therapeutic target in Joint Contractures.
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Chaperonin containing T-complex polypeptide subunit eta is a potential marker of Joint Contracture: an experimental study in the rat
Cell stress & chaperones, 2015Co-Authors: Zhe Wang, Junqi Huang, Jianhua Ren, Kun WangAbstract:Joint Contracture is a fibroproliferative disorder that restricts Joint mobility, resulting in tissue degeneration and deformity. However, the etiology of Joint Contracture is still unknown. Chaperonin containing T-complex polypeptide subunit eta (CCT-eta) is reported to increase in fibrotic diseases. The purpose of this study was to investigate whether CCT-eta is implicated in Joint Contracture and to determine the role of CCT-eta in the progression of Joint Contracture by analyzing a rat model. We immobilized the left knee Joint of rat by internal fixation for 8 weeks. The non-immobilized right leg served as a control. The range of motion (ROM) of the knee was investigated. Fibroblasts were obtained from the posterior Joint capsule of the Joints. The outcome was followed by quantitative real-time polymerase chain reaction (qRT-PCR), Western blot, fibroblast migration assay, and collagen assay. The effect of CCT-eta on the functions of fibroblasts was observed by utilizing a short inhibitory RNA (siRNA) targeting CCT-eta. The ROM of the immobilized Joints was significantly limited compared to the contralateral Joints (p < 0.05). Fibroblasts derived from the contractive Joints showed higher mRNA and protein expressions of CCT-eta in parallel with alpha-smooth muscle actin (α-SMA) compared to the cells from the contralateral knees (p < 0.05). siRNA-mediated downregulation of CCT-eta inhibited the expressions of both CCT-eta and α-SMA. Moreover, the reduction of CCT-eta also significantly decreased fibroblast functions such as cell mobility and collagen synthesis (all p < 0.05). Our findings indicate that CCT-eta appears to be a potential marker of Joint Contracture disease.
Quan-bing Zhang - One of the best experts on this subject based on the ideXlab platform.
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effect of ultrashort wave treatment on Joint dysfunction and muscle atrophy in a rabbit model of extending knee Joint Contracture enhanced expression of myogenic differentiation
Knee, 2020Co-Authors: Feng Wang, Quan-bing Zhang, Yun Zhou, Peng-peng Huang, Ying A Liu, Yi LiuAbstract:Abstract Objective To investigate the effects of ultrashort wave treatment on Joint dysfunction and muscle atrophy in a rabbit model of extending knee Joint Contracture. Methods Forty rabbits were randomly divided into eight groups. In group C, the left knee Joint was not fixed. In group I-8, the left knee Joint was only fixed for eight weeks. In groups R-1, R-2, and R-4, the left knee Joint was fixed for eight weeks before the rabbits underwent one, two, and four weeks of self-recovery, respectively. In groups T-1, T-2, and T-4, the left knee Joint was fixed for eight weeks before the rabbits underwent one, two, and four weeks of ultrashort wave treatment, respectively. The degree of total Contracture and myogenic Contracture were measured, the cross-sectional area (CSA) and protein levels for myogenic differentiation (MyoD) of the rectus femoris were evaluated. Results There was a tendency toward a reduced degree of total and myogenic Contracture, and also a tendency toward an increased CSA of the rectus femoris and increased protein levels for MyoD after both self-recovery and ultrashort wave treatment. The ultrashort wave was more effective than self-recovery in reducing the total and myogenic Contracture, and increasing the CSA and MyoD protein levels of the rectus femoris. Conclusions Ultrashort wave treatment may ameliorate Joint dysfunction and muscle atrophy by upregulating the expression of MyoD protein in a rabbit model of extending knee Joint Contracture.
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The mechanisms and treatments of muscular pathological changes in immobilization-induced Joint Contracture: A literature review.
Chinese journal of traumatology = Zhonghua chuang shang za zhi, 2019Co-Authors: Feng Wang, Quan-bing Zhang, Yun Zhou, Shuang Chen, Peng-peng Huang, Yi LiuAbstract:The clinical treatment of Joint Contracture due to immobilization remains difficult. The pathological changes of muscle tissue caused by immobilization-induced Joint Contracture include disuse skeletal muscle atrophy and skeletal muscle tissue fibrosis. The proteolytic pathways involved in disuse muscle atrophy include the ubiquitin-proteasome-dependent pathway, caspase system pathway, matrix metalloproteinase pathway, Ca2+-dependent pathway and autophagy-lysosomal pathway. The important biological processes involved in skeletal muscle fibrosis include intermuscular connective tissue thickening caused by transforming growth factor-β1 and an anaerobic environment within the skeletal muscle leading to the induction of hypoxia-inducible factor-1α. This article reviews the progress made in understanding the pathological processes involved in immobilization-induced muscle Contracture and the currently available treatments. Understanding the mechanisms involved in immobilization-induced Contracture of muscle tissue should facilitate the development of more effective treatment measures for the different mechanisms in the future.
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The mechanisms and treatments of muscular pathological changes in immobilization-induced Joint Contracture: A literature review
Elsevier, 2019Co-Authors: Feng Wang, Quan-bing Zhang, Yun Zhou, Shuang Chen, Peng-peng Huang, Yi LiuAbstract:The clinical treatment of Joint Contracture due to immobilization remains difficult. The pathological changes of muscle tissue caused by immobilization-induced Joint Contracture include disuse skeletal muscle atrophy and skeletal muscle tissue fibrosis. The proteolytic pathways involved in disuse muscle atrophy include the ubiquitin-proteasome-dependent pathway, caspase system pathway, matrix metalloproteinase pathway, Ca2+-dependent pathway and autophagy-lysosomal pathway. The important biological processes involved in skeletal muscle fibrosis include intermuscular connective tissue thickening caused by transforming growth factor-β1 and an anaerobic environment within the skeletal muscle leading to the induction of hypoxia-inducible factor-1α. This article reviews the progress made in understanding the pathological processes involved in immobilization-induced muscle Contracture and the currently available treatments. Understanding the mechanisms involved in immobilization-induced Contracture of muscle tissue should facilitate the development of more effective treatment measures for the different mechanisms in the future. Keywords: Immobilization-induced Joint Contracture, Disuse skeletal muscle atrophy, Skeletal muscle fibrosis, Treatmen
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Rabbit Model of Extending Knee Joint Contracture: Progression of Joint Motion Restriction and Subsequent Joint Capsule Changes after Immobilization.
Journal of Knee Surgery, 2018Co-Authors: Yun Zhou, Quan-bing Zhang, Huazhang Zhong, Yi Liu, Jue Hua JingAbstract:This study aimed to develop a rabbit model of knee Contracture in extension and investigate the natural history of motion loss and time-dependent changes in the Joint capsule after immobilization. We immobilized the unilateral knee Joints of 32 rabbits by maintaining the knee Joint in a plaster cast at full extension. Eight rabbits were euthanized at 2, 4, 6, and 8 weeks after casting, respectively, and the lower extremities were disarticulated at the hip Joint. Eight control group rabbits that did not undergo immobilization were also examined. We assessed the progression of Joint Contracture by measuring the Joint range of motion, evaluating the histologic alteration of the capsule, and assessing the mRNA levels of transforming growth factor β1 (TGF-β1) in the anterior and posterior Joint capsules. After 2 weeks of Joint immobilization, the knee Joint range of motion was limited, the synovial membrane of the suprapatellar and posterior Joint capsules was thickened, the collagen deposition was increased, and the mRNA levels of TGF-β1 were elevated in the anterior and posterior Joint capsules. These changes progressed rapidly until 6 weeks of immobilization and may advance slowly after 6 weeks. Joint Contracture developed at the early stage of immobilization and progressed over time. The changes in the anterior and posterior Joint capsules after Joint immobilization may contribute to the limitation in flexion. The elevated mRNA expression of TGF-β1 may be related to Joint capsule fibrosis and may be one of the causes of Joint Contracture.
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effect of stretching combined with ultrashort wave diathermy on Joint function and its possible mechanism in a rabbit knee Contracture model
American Journal of Physical Medicine & Rehabilitation, 2017Co-Authors: Quan-bing Zhang, Yun Zhou, Huazhang Zhong, Yi LiuAbstract:Objective The aim of this study was to investigate the therapeutic effect of stretching combined with ultrashort wave on Joint Contracture and explore its possible mechanism. Design Thirty-two rabbits underwent unilateral immobilization of a knee Joint at full extension to cause Joint Contracture. At 6 wks after immobilization, the rabbits were randomly divided into the following four groups: natural recovery group, stretching treatment group, ultrashort wave treatment group, and combined treatment group. For comparison, eight control group animals of corresponding age were also examined. The effect of stretching and ultrashort wave treatment on Joint Contracture was assessed by measuring the Joint range of motion, evaluating the collagen deposition of Joint capsule and assessing the mRNA and protein levels for transforming growth factor β1 in the Joint capsule. Results The combined treatment group led to the best recovery of Joint function. The combined treatment with stretching and ultrashort wave was more effective than stretching or ultrashort wave treatment alone against the synovial thickening of suprapatellar Joint capsule, the collagen deposition of anterior Joint capsule, and the elevated expression of transforming growth factor β1 in the Joint capsule. Conclusions Stretching combined with ultrashort wave treatment was effective in improving Joint range of motion, reducing the biomechanical, histological, and molecular manifestations of Joint capsule fibrosis in a rabbit model of extending Joint Contracture.
