scholarly journals Circular RNA mmu_circ_0001598 Contributes to IL-1β-Induced Osteoarthritis Progression by Regulating miR-127-3p

2021 ◽  
Vol 2021 ◽  
pp. 1-8
Author(s):  
Xierenguli Apizi ◽  
Dilibaier Talifujiang ◽  
Aziguli Kasimu ◽  
Xue Zhang ◽  
Aibibula Yiming ◽  
...  
Keyword(s):  
Cruciate Ligament ◽  
Critical Role ◽  
Cartilage Degeneration ◽  
Circular Rna ◽  
Cartilage Tissue ◽  
Circular Rnas ◽  
Chondrocyte Proliferation ◽  
Osteoarthritis Progression ◽  
Anterior Cruciate

Osteoarthritis (OA), a chronic disease characterized by articular cartilage degeneration, is a leading cause of disability and pain worldwide. Accumulating evidence indicates that circular RNAs (circRNAs) play a critical role in various diseases, but the function of circRNAs in OA remains largely unknown. In this study, we found that circ_0001598 was significantly upregulated in chondrocytes treated with IL-1β and in cartilage tissue from mice with severed anterior cruciate ligament surgery (ACLT) induced OA models. Interference with circ_0001598 in vitro restored IL-1β-induced chondrocyte proliferation and apoptosis. Silencing circ_0001598 significantly alleviated ACLT-induced OA in mice. Mechanistically, knockdown of circ_0001598 affected chondrocyte proliferation, apoptosis, and matrix degradation by regulating miR-127-3p. Taken together, our results demonstrate the fundamental role of circ_0001598 and provide new ideas for the prevention and treatment of osteoarthritis.

scholarly journals α2-Macroglobulin-Rich Serum As a Master Inhibitor of Inflammatory Factors Attenuates Cartilage Degeneration in a Mini Pig Model of Osteoarthritis Induced By “Idealized” Anterior Cruciate Ligament Reconstruction

2021 ◽  
Author(s):  
Ruipeng Zhao ◽  
Xiaochun Wei ◽  
Chengming Zhang ◽  
Hongru Wu ◽  
Chuan Xiang ◽  
...  
Keyword(s):  
Anterior Cruciate Ligament ◽  
Cruciate Ligament ◽  
Cartilage Degeneration ◽  
Mature Female ◽  
Inflammatory Factors ◽  
Post Surgery ◽  
Α2 Macroglobulin ◽  
Anterior Cruciate

Abstract Background: α2-Macroglobulin (α2M) is important for chondral protection in post-traumatic osteoarthritis (PTOA). However, its injection into xenogeneic joint cavities has safety hazards, limiting clinical applications. Exploring serum α2M-enriching strategies and the therapeutic effect and mechanism of α2M-rich serum (α2MRS) autologous joint injection to treat PTOA has significant value.Methods: A unique filtration process was used to concentrate α2M from serum. Human osteoarthritic chondrocytes induced with interleukin (IL)-1β were used to evaluate catabolic enzymes, cell proliferation, apoptosis, and gene expression 24h after α2MRS treatment. Eighteen mature female mini pigs were randomized to three groups, sham (n = 6), “idealized” anterior cruciate ligament autograft reconstruction (IACL-R) (n = 6), and IACL-R+α2MRS (n = 6). Expression of inflammatory factors in the synovial fluid (SF) was measured using Luminex assays. Gait features were recorded using the Tekscan Walkway system. The extent of PTOA progression was evaluated using imaging, real-time PCR , and histology 3 months post-surgery.Results: The α2M concentration in α2MRS was higher than that in human and mini pig serum, respectively. In vitro, α2MRS significantly promoted human chondrocyte proliferation (p < 0.001) and reduced apoptosis (p < 0.001) and chondrocyte catabolic cytokine gene transcription (p < 0.001) and secretion (p < 0.001). In vivo, SF concentrations of all tested inflammatory factors were significantly lower in the IACL-R+α2MRS group than in the IACL-R group (p < 0.001). All gait parameters in the IACL-R+α2MRS group returned to normal significantly early compared to those in the IACL-R group (p < 0.05). Imaging , histology, and biochemistry data showed that cartilage degeneration in the IACL-R+α2MRS group was significantly diminished relative to that in the IACL-R group (p < 0.001).Conclusion: Injecting α2MRS into the joint cavity after IACL-R can significantly delay articular cartilage degeneration.

scholarly journals CircECE1 activates energy metabolism in osteosarcoma by stabilizing c-Myc

2020 ◽  
Vol 19 (1) ◽  
Author(s):  
Shuying Shen ◽  
Teng Yao ◽  
Yining Xu ◽  
Deguang Zhang ◽  
Shunwu Fan ◽  
...  
Keyword(s):  
Energy Metabolism ◽  
Warburg Effect ◽  
Critical Role ◽  
Circular Rna ◽  
Molecular Therapy ◽  
Circular Rnas ◽  
Rna Immunoprecipitation ◽  
The Warburg Effect

Abstract Background Osteosarcoma (OS) is the most common malignant bone tumor and has a poor prognosis. The potential involvement of circular RNAs (circRNAs) in OS progression remains unexplored. Here, we report that CircECE1, a circular RNA derived from human ECE1, plays a critical role in energy metabolism in OS. Methods The RIP chip sequence assay was performed to confirm CircECE1, through overexpression or knockdown of CircECE1 to verify its function in 143B and U2OS. RNA immunoprecipitation and immunoprecipitation were used to verify CircECE1’s regulation of protein c-Myc and co- immunoprecipitation was used to verified the competitive binding relationship between CircECE1 and SPOP. The influence of CircECE1 on energy metabolism was evaluated by seahorse experiment, western blot, and immunohistochemistry. Results We found that CircECE1 is highly expressed in OS tissues and cells and that CircECE1 knockdown suppresses tumor proliferation and metastasis both in vitro and in vivo. Further, CircECE1 significantly promotes glucose metabolism in OS cells in vitro and in vivo. Mechanistically, CircECE1 interacts with c-Myc to prevent speckle-type POZ-mediated c-Myc ubiquitination and degradation. C-Myc inhibits thioredoxin binding protein (TXNIP) transcription and subsequently activates the Warburg effect. Conclusions CircECE1 regulates the Warburg effect through the c-Myc/TXNIP axis. CircECE1 mediated signal transduction plays a important role in OS process and energy metabolism. These findings may identify novel targets for OS molecular therapy.

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 The circular RNA circZFR phosphorylates Rb promoting cervical cancer progression by regulating the SSBP1/CDK2/cyclin E1 complex

2021 ◽  
Vol 40 (1) ◽  
Author(s):  
Mingyi Zhou ◽  
Zhuo Yang ◽  
Danbo Wang ◽  
Peng Chen ◽  
Yong Zhang
Keyword(s):  
Cervical Cancer ◽  
Cancer Progression ◽  
Cell Cycle Progression ◽  
Critical Role ◽  
Circular Rna ◽  
Circular Rnas ◽  
Cyclin E1 ◽  
Normal Tissues ◽  
Exact Function ◽  
Potential Biomarker

Abstract Background As a novel type of non-coding RNA, circular RNAs (circRNAs) play a critical role in the initiation and development of various diseases, including cancer. However, the exact function of circRNAs in human cervical cancer remains largely unknown. Methods We identified the circRNA signature of upregulated circRNAs between cervical cancer and paired adjacent normal tissues. Using two different cohorts and GEO database, a total of six upregulated circRNAs were identified with a fold change > 2, and P < 0.05. Among these six circRNAs, hsa_circ_0072088 (circZFR) was the only exonic circRNA significantly overexpressed in cervical cancer. Functional experiments were performed to investigate the biological function of circZFR. CircRNA pull-down, circRNA immunoprecipitation (circRIP) and Co-immunoprecipitation (Co-IP) assays were executed to investigate the molecular mechanism underlying the function of circZFR. Results Functionally, circZFR knockdown represses the proliferation, invasion, and tumor growth. Furthermore, circRNA pull-down experiments combined with mass spectrometry unveil the interactions of circZFR with Single-Stranded DNA Binding Protein 1 (SSBP1). Mechanistically, circZFR bound with SSBP1, thereby promoting the assembly of CDK2/cyclin E1 complexes. The activation of CDK2/cyclin E1 complexes induced p-Rb phosphorylation, thus releasing activated E2F1 leading to cell cycle progression and cell proliferation. Conclusion Our findings provide the first evidence that circZFR is a novel onco-circRNA and might be a potential biomarker and therapeutic target for cervical cancer patients.

scholarly journals Whether sutures reduce the graft laceration caused by interference screw in anterior cruciate ligament reconstruction? A biomechanical study in vitro

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Yuanjun Teng ◽  
Xiaohui Zhang ◽  
Lijun Da ◽  
Jie Hu ◽  
Hong Wang ◽  
...  
Keyword(s):  
Acl Reconstruction ◽  
Cruciate Ligament ◽  
Interference Screw ◽  
Biomechanical Study ◽  
Interference Screws ◽  
Suture Group ◽  
Anterior Cruciate ◽  
Biomechanical Tests ◽  
Single Insertion

Abstract Background Interference screw is commonly used for graft fixation in anterior cruciate ligament (ACL) reconstruction. However, previous studies had reported that the insertion of interference screws significantly caused graft laceration. The purposes of this study were to (1) quantitatively evaluate the graft laceration from one single insertion of PEEK interference screws; and (2) determine whether different types of sutures reduced the graft laceration after one single insertion of interference screws in ACL reconstruction. Methods The in-vitro ACL reconstruction model was created using porcine tibias and bovine extensor digitorum tendons of bovine hind limbs. The ends of grafts were sutured using three different sutures, including the bioabsorbable, Ethibond and ultra-high molecular weight polyethylene (UHMWPE) sutures. Poly-ether-ether-ketone (PEEK) interference screws were used for tibial fixation. This study was divided into five groups (n = 10 in each group): the non-fixed group, the non-sutured group, the absorbable suture group, the Ethibond suture group and the UHMWPE suture group. Biomechanical tests were performed using the mode of pull-to-failure loading tests at 10 mm/min. Tensile stiffness (newtons per millimeter), energy absorbed to failure (in joules) and ultimate load (newtons) were recorded for analysis. Results All prepared tendons and bone specimens showed similar characteristics (length, weight, and pre-tension of the tendons, tibial bone mineral density) among all groups (P > 0.05). The biomechanical tests demonstrated that PEEK interference screws significantly caused the graft laceration (P < 0.05). However, all sutures (the bioabsorbable, Ethibond and UHMWPE sutures) did not reduce the graft laceration in ACL reconstruction (P > 0.05). Conclusions Our biomechanical study suggested that the ultimate failure load of grafts was reduced of approximately 25 % after one single insertion of a PEEK interference screw in ACL reconstruction. Suturing the ends of the grafts using different sutures (absorbable, Ethibond and UHMWPE sutures) did not decrease the graft laceration caused by interference screws.

Effect of Remnant-Preserving Reconstruction of Acute Anterior Cruciate Ligament Injuries in a Rabbit Model: Histological and Biomechanical Analysis

2022 ◽  
Vol 12 (5) ◽  
pp. 897-906
Author(s):  
XiaoChen Ju ◽  
Hao Chai ◽  
Sasirekha Krishnan ◽  
Abinaya Jaisankar ◽  
Murugan Ramalingam ◽  
...  
Keyword(s):  
Anterior Cruciate Ligament ◽  
Articular Cartilage ◽  
Acl Reconstruction ◽  
Bone Healing ◽  
Cruciate Ligament ◽  
Cartilage Degeneration ◽  
Remnant Preservation ◽  
Model Animal ◽  
Anterior Cruciate ◽  
Articular Cartilage Degeneration

Acute anterior cruciate ligament (ACL) is a key structure that stabilizes knee joints. The objective of this research is to investigate the influence of ligament remnants preserved on the tendon-bone healing following ACL reconstruction and to examine postoperative articular cartilage degeneration in rabbit as a model animal. Sixty New Zealand rabbits are randomly divided into an ACL reconstruction without remnant preservation group (Group A; n = 30) or ACL reconstruction with remnant preservation group (Group B; n = 30). The expression of HIF-1α, VEGF, and micro vessel density (MVD) in the transplanted tendon was detected by immunohistochemical staining at week 6 and 12 after the operation. The signal intensity of the transplanted tendon was observed by MRI scanning, and the width of the bone tunnel was measured by CT scanning at week 6 and 12 after the operation. The graft biomechanics was tested 12 weeks after the operation. The JNK and MMP-13 expression levels were compared to analyze the cartilage degeneration of the knee at week 12 after the operation. The experimental results were analyzed and showed that the remnant-preserving ACL reconstruction is beneficial for bone healing of the tendon in rabbits, but ACL reconstruction with or without ligament remnants preserved will not affect knee articular cartilage degeneration post-surgery.

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