Therapeutic effect of intra‐articular injection of ribbon‐type decoy oligonucleotides for hypoxia inducible factor‐1 on joint contracture in an immobilized knee animal model

Sotobayashi, Daisuke; Kawahata, Hirohisa; Anada, Natsuki; Ogihara, Toshio; Morishita, Ryuichi; Aoki, Motokuni

doi:10.1002/jgm.2891

Cited by 21 publications

(17 citation statements)

References 52 publications

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“…Previous studies have shown an immobilization‐related increase in connective tissue, which is consistent with our results. The reduction of ROM in the immobilized knee joint accompanied by synovial hypertrophy in the mouse model has been demonstrated . Moreover, previous studies found that the extensibility of the joint capsule depends on its thickness .…”

Section: Discussionmentioning

confidence: 85%

“…Previous studies suggested that immobilization induces joint capsule fibrosis . Higher amounts of type I collagen have been reported in the capsules of immobilized knees, and synovial hypertrophy with fibrosis in the joint capsule has been observed after immobilization . These studies suggest that joint capsule fibrosis may be a primary cause of pathology in joint contractures.…”

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confidence: 70%

“…Several studies examined changes in the expression of type I and III collagen—the major structural collagens of the joint capsule—to determine the pathology of joint capsule fibrosis . Although these studies utilized immunohistochemical, biochemical, and molecular biological methods, the pathology of joint capsule fibrosis could not be conclusively determined, as the findings were not in agreement . Other studies examined factors related to the development of fibrosis (e.g., the role of cytokines, and inflammatory and hypoxic conditions) in a rat knee joint contracture model.…”

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confidence: 99%

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Effects of joint immobilization on changes in myofibroblasts and collagen in the rat knee contracture model

et al. 2017

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The purpose of this study was to examine the time-dependent changes in the development of joint capsule fibrosis and in the number of myofibroblasts in the joint capsule after immobilization, using a rat knee contracture model. Both knee joints were fixed in full flexion for 1, 2, and 4 weeks (immobilization group). Untreated rats were bred for each immobilization period (control group). Histological analysis was performed to evaluate changes in the amount and density of collagen in the joint capsule. The changes in type I and III collagen mRNA were examined by in situ hybridization. The number of myofibroblasts in the joint capsule was assessed by immunohistochemical methods. In the immobilization group, the amount of collagen increased within 1 week and the density of collagen increased within 2 weeks, as compared with that in the control group. Type I collagen mRNA-positive cell numbers in the immobilization group increased at all time points. However, type III collagen mRNA-positive cell numbers did not increase. Myofibroblasts in the immobilization group significantly increased compared with those in the control group at all time points, and they increased significantly with the period of immobilization. These results suggest that joint capsule fibrosis with overexpression of type I collagen occurs and progresses within 1 week after immobilization, and an increase in myofibroblasts is related to the mechanism of joint capsule fibrosis. The findings suggest the need for a treatment targeting accumulation of type I collagen associated with an increase in myofibroblasts. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:1998-2006, 2017.

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Section: Discussionmentioning

confidence: 85%

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confidence: 70%

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confidence: 99%

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Effects of joint immobilization on changes in myofibroblasts and collagen in the rat knee contracture model

et al. 2017

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“…In the existing studies on medical inhibition of the development of joint contracture (Table 2), an improvement of the range of motion could be achieved mostly after intraarticular application of the respective active agents. 16,17,64,[95][96][97][98][99][100][101][102][103][104] Although these results constitute an opportunity for the development of a medical treatment of patients with PTJS, the intraarticular application is unfavorable for a number of reasons: i) it is a painful and invasive procedure for the patient, ii) it bears the risk of septic arthritis, iii) it might damage the articular cartilage by chondrotoxic effects or iv) weaken the capsule and ligaments of the knee. [105][106][107] Based on the rabbit models of PTJS of Hildebrand et al and Nesterenko et al, our group established a rat model of PTJS of the knee joint that included a rupture of the posterior joint capsule, a hemarthrosis, an intraarticular bone damage and a temporary fixation of the joint.…”

Section: Atorvastatin Inferior Capsulementioning

confidence: 99%

<p>Effects of losartan and atorvastatin on the development of early posttraumatic joint stiffness in a rat model</p>

Baranowski

Schlemmer

Förster

et al. 2019

DDDT

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Background After a trauma, exuberant tissue healing with fibrosis of the joint capsule can lead to posttraumatic joint stiffness (PTJS). Losartan and atorvastatin have both shown their antifibrotic effects in different organ systems. Objective The purpose of this study was the evaluation of the influence of losartan and atorvastatin on the early development of joint contracture. In addition to joint angles, the change in myofibroblast numbers and the distribution of bone sialoprotein (BSP) were assessed. Study design and methods In this randomized and blinded experimental study with 24 rats, losartan and atorvastatin were compared to a placebo. After an initial joint injury, rat knees were immobilized with a Kirschner wire. Rats received either losartan, atorvastatin or a placebo orally daily. After 14 days, joint angle measurements and histological assessments were performed. Results Losartan increased the length of the inferior joint capsule. Joint angle and other capsule length measurements did not reveal significant differences between both drugs and the placebo. At cellular level both losartan and atorvastatin reduced the total number of myofibroblasts (losartan: 191±77, atorvastatin: 98±58, placebo: 319±113 per counting field, p <0.01) and the percentage area of myofibroblasts (losartan: 2.8±1.8% [ p <0.05], atorvastatin: 2.5±1.7% [ p <0.01], vs control [6.4±4%], respectively). BSP was detectable in equivalent amounts in the joint capsules of all groups with only a trend toward a reduction of the BSP-stained area by atorvastatin. Conclusion Both atorvastatin and losartan reduced the number of myofibroblasts in the posterior knee joint capsule of rat knees 2 weeks after trauma and losartan increased the length of the inferior joint capsule. However, these changes at the cellular level did not translate an increase in range of motion of the rats´ knee joints during early contracture development.

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“…In a ribbon-type (dumbbell-type) decoy ODN, both double-stranded termini of the decoy ODN are linked by a circular structure of nucleic acids, because degradation of decoy ODN by nuclease begins at the site where ODN ends. 52,85,86) Indeed, our previous study reported that ribbon-type decoy ODN against NFκB and ets could inhibit AAA progression in an elastase-induced rat AAA model despite systemic administration. 87) In addition, our recent study and other studies have demonstrated that sense and antisense strands of decoy ODN were linked with a chemical spacer instead of nucleic acids.…”

Section: Structural Modification Of Decoy Odn and Delivery Systemmentioning

confidence: 99%

Molecular Pharmacological Approaches for Treating Abdominal Aortic Aneurysm

Miyake

Kurashiki

et al. 2019

Annals of Vascular Diseases

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Abdominal aortic aneurysm (AAA) is considered to be a potent life-threatening disorder in elderly individuals. Although many patients with a small AAA are detected during routine abdominal screening, there is no effective therapeutic option to prevent the progression or regression of AAA in the clinical setting. Recent advances in molecular biology have led to the identification of several important molecules, including microRNA and transcription factor, in the process of AAA formation. Regulation of these factors using nucleic acid drugs is expected to be a novel therapeutic option for AAA. Nucleic acid drugs can bind to target factors, mRNA, microRNA, and transcription factors in a sequence-specific fashion, resulting in a loss of function of the target molecule at the transcriptional or posttranscriptional level. Of note, inhibition of a transcription factor using a decoy strategy effectively suppresses experimental AAA formation, by regulating the expression of several genes associated with the disease progression. This review focuses on recent advances in molecular therapy of using nucleic acid drugs to treat AAA.

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Therapeutic effect of intra‐articular injection of ribbon‐type decoy oligonucleotides for hypoxia inducible factor‐1 on joint contracture in an immobilized knee animal model

Cited by 21 publications

References 52 publications

Effects of joint immobilization on changes in myofibroblasts and collagen in the rat knee contracture model

Effects of joint immobilization on changes in myofibroblasts and collagen in the rat knee contracture model

<p>Effects of losartan and atorvastatin on the development of early posttraumatic joint stiffness in a rat model</p>

Molecular Pharmacological Approaches for Treating Abdominal Aortic Aneurysm

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