scholarly journals Hyaluronic Acid versus Alpha-2-Macroglobulin Intra-Articular Injections for Amelioration of Knee Posttraumatic Osteoarthritis: A Rat Model

2020 ◽  
Author(s):  
Shaowei Wang ◽  
Mengbo Zhu ◽  
Yanjing Guo ◽  
Ruijia Yang ◽  
Yaqiong Chang ◽  
...  
Keyword(s):  
Hyaluronic Acid ◽  
Articular Cartilage ◽  
Synovial Fluid ◽  
Rat Model ◽  
Cruciate Ligament ◽  
Cartilage Damage ◽  
Cartilage Degeneration ◽  
Protective Effects ◽  
Significant Difference ◽  
Histological Staining

Abstract Background: The study was performed to evaluate whether intra-articular injection of A2M has better effect than current commonly used Hyaluronic Acid (HA) injection therapy to attenuate cartilage degeneration in a rat anterior cruciate ligament transection (ACLT) osteoarthritis (OA) model.Method: In vivo effects of A2M and HA on cartilage degeneration were evaluated in rat surgery induced ACLT OA models. 100 rats were randomly divided into four groups: (a) Sham surgery + saline (Sham + S), (b) ACLT + A2M, (c) ACLT+HA, or (d) ACLT + saline (ACLT+S). The animals were sacrificed at 12 weeks after surgery. Histological staining was performed to assess cartilage damage. The concentration of MMP-13 and sGAG in synovial fluid lavages was measured using ELISA and spectrophotometric quantitative determination. OA-related gene expression was quantified by qPCR.Result: Indian ink staining showed that articular cartilage surface treated by A2M was relatively intact compared with the animals treated by ACLT with saline or HA injection. Histological staining indicated that early supplemental intra-articular injection of A2M attenuated OA pathogenesis in the rat ACLT model compared with the animals treated with saline and HA. However, supplemental intra-articular injection of HA showed no significant effect on cartilage protection for post traumatic OA compared with saline treatment. Elisa results showed A2M reduced the concentration of MMP-13 in synovial fluid compared with HA treatment group and other groups. RT-qPCR indicated that supplemental intra-articular A2M inhibits catabolism and enhances anabolic metabolism, while there was no significant difference in the expression of OA-related genes between ACLT+HA group and ACLT+S group. Conclusion: In rat model, intra-articular injection of A2M had obvious protective effects on cartilage degeneration compared with HA treatment. Major indexes of joint degeneration decreased, providing strong evidence for its intra-articular inhibitory effect. Meanwhile, we found no significant alleviation of articular cartilage pathogenesis in HA treated group, which suggests that the efficacy of HA is questionable and possibly transient, although it is extensively used to improve syndromes.

scholarly journals LncRNA CRNED Hinders The Progression of Osteoarthritis By Epigenetic Regulation of DACT1

2021 ◽  
Author(s):  
Ziqi Zhang ◽  
Pei Yang ◽  
Chunsheng Wang ◽  
Run Tian
Keyword(s):  
Rat Model ◽  
Epigenetic Modification ◽  
Colorectal Neoplasia ◽  
Cruciate Ligament ◽  
Cartilage Damage ◽  
Cartilage Degeneration ◽  
Downstream Target ◽  
Age Related

Abstract Osteoarthritis (OA) is mainly characterized by articular cartilage degeneration, synovial fibrosis, and inflammation. LncRNA CRNED (colorectal neoplasia differentially expressed) has been reported to be down-regulated in age-related OA, but its role in injury-induced OA needs to be further explored. In this study, an OA rat model was established by using anterior cruciate ligament transection, and the adenovirus-mediated CRNED overexpression (Ad-CRNED) or DACT1 (dapper antagonist of catenin-1) interference (sh-DACT1) vectors were injected into the rat model via tail vein. Besides, chondrocyte‑like ATDC5 cells were treated with IL-1β (10 ng/mL) to simulate OA conditions in vitro. We found that overexpression of CRNED alleviated cartilage damage and synovitis in OA rats, and suppressed IL-1β-induced apoptosis, inflammation, and extracellular matrix (ECM) degradation in chondrocyte‑like ATDC5 cells, while silencing DACT1 effectively antagonized the protective effect of CRNED both in vivo and in vitro. Mechanism studies revealed that DACT1 could act as a downstream target of CRNED. By recruiting p300, CRNED promoted the enrichment of H3K27ac in the DACT1 promoter, thus promoting DACT1 transcription. In addition, CRNED hindered the activation of the Wnt/β-catenin pathway in IL-1β-stimulated cells by inducing DACT1 expression. In conclusion, CRNED promoted DACT1 expression through epigenetic modification and restrained the activation of Wnt/β-catenin signaling to impede the progression of OA.

scholarly journals Halofuginone attenuates osteoarthritis by inhibition of TGF-β activity and H-type vessel formation in subchondral bone

2015 ◽  
Vol 75 (9) ◽  
pp. 1714-1721 ◽  
Author(s):  
Zhuang Cui ◽  
Janet Crane ◽  
Hui Xie ◽  
Xin Jin ◽  
Gehua Zhen ◽  
...  
Keyword(s):  
Articular Cartilage ◽  
Subchondral Bone ◽  
Bone Remodelling ◽  
Cruciate Ligament ◽  
Cartilage Degeneration ◽  
Research Society ◽  
Preventive Therapy ◽  
Protective Effects ◽  
Anterior Cruciate ◽  
Articular Cartilage Degeneration

ObjectivesExamine whether osteoarthritis (OA) progression can be delayed by halofuginone in anterior cruciate ligament transection (ACLT) rodent models.Methods3-month-old male C57BL/6J (wild type; WT) mice and Lewis rats were randomised to sham-operated, ACLT-operated, treated with vehicle, or ACLT-operated, treated with halofuginone. Articular cartilage degeneration was graded using the Osteoarthritis Research Society International (OARSI)-modified Mankin criteria. Immunostaining, flow cytometry, RT-PCR and western blot analyses were conducted to detect relative protein and RNA expression. Bone micro CT (μCT) and CT-based microangiography were quantitated to detect alterations of microarchitecture and vasculature in tibial subchondral bone.ResultsHalofuginone attenuated articular cartilage degeneration and subchondral bone deterioration, resulting in substantially lower OARSI scores. Specifically, we found that proteoglycan loss and calcification of articular cartilage were significantly decreased in halofuginone-treated ACLT rodents compared with vehicle-treated ACLT controls. Halofuginone reduced collagen X (Col X), matrix metalloproteinase-13 and A disintegrin and metalloproteinase with thrombospondin motifs 5 (ADAMTS 5) and increased lubricin, collagen II and aggrecan. In parallel, halofuginone-attenuated uncoupled subchondral bone remodelling as defined by reduced subchondral bone tissue volume, lower trabecular pattern factor (Tb.pf) and increased thickness of subchondral bone plate compared with vehicle-treated ACLT controls. We found that halofuginone exerted protective effects in part by suppressing Th17-induced osteoclastic bone resorption, inhibiting Smad2/3-dependent TGF-β signalling to restore coupled bone remodelling and attenuating excessive angiogenesis in subchondral bone.ConclusionsHalofuginone attenuates OA progression by inhibition of subchondral bone TGF-β activity and aberrant angiogenesis as a potential preventive therapy for OA.

Intra-Articular Biocompatibility of Multistranded, Long-Chain Polyethylene Suture Tape in a Canine ACL Model

2018 ◽  
Vol 32 (06) ◽  
pp. 525-531 ◽  
Author(s):  
Patrick A. Smith ◽  
Chantelle C. Bozynski ◽  
Keiichi Kuroki ◽  
Sarah M. Henrich ◽  
Coen A. Wijdicks ◽  
...  
Keyword(s):  
Articular Cartilage ◽  
Postoperative Complications ◽  
Acl Reconstruction ◽  
Cruciate Ligament ◽  
Cartilage Damage ◽  
Cartilage Degeneration ◽  
Case Scenario ◽  
Worst Case ◽  
Study Results ◽  
Suture Tape

AbstractThe purpose of this study was to assess intra-articular use of a nonabsorbable braided suture tape for its biocompatibility when implanted adjacent to the native anterior cruciate ligament (ACL) in a canine model. Establishing biocompatibility of suture tape in the knee is an important foundational step for clinicians considering use of suture tape augmentation for ACL reconstruction or repair. The study hypothesis was that a nonabsorbable braided suture tape would be biocompatible in the knee with no resultant adverse functional consequences, and no significant intra-articular synovial reactions or articular cartilage degeneration attributable to direct exposure to the suture tape, whether intact or transected. Nonabsorbable braided suture tape was arthroscopically implanted adjacent to the native ACL of dogs (n = 6). The suture was intact in half of the dogs and was transected in the other half as a “worst-case” scenario. Dogs were assessed for postoperative complications and morbidity. Arthroscopic grading of synovium and cartilage was performed at 4 and 6 months. Histologic assessments were performed at the 6-month endpoint and compared with the ACL partial tear (n = 9) and ACL reconstruction (n = 5) cohorts as well as historical sham controls. No postoperative complications were noted. No animal developed lameness or clinical dysfunction, and there were no severe inflammatory or immune responses, cartilage erosions, or premature osteoarthritis noted. Arthroscopic assessments revealed no to mild synovitis and no apparent cartilage damage in either group. Histologically, both the intact and transected suture tape groups were associated with significantly (p ≤ 0.05) less synovial and articular cartilage pathology compared with the partial ACL transection and patellar bone–tendon–bone ACL autograft reconstruction cohorts, and matched historical sham controls. The hypothesis was accepted as study results support the biocompatibility of suture tape in the canine knee.

scholarly journals Genetic Deletion of Interleukin-15 Is Not Associated with Major Structural Changes Following Experimental Post-Traumatic Knee Osteoarthritis in Rats

2021 ◽  
Vol 11 (15) ◽  
pp. 7118
Author(s):  
Ermina Hadzic ◽  
Garth Blackler ◽  
Holly Dupuis ◽  
Stephen James Renaud ◽  
Christopher Thomas Appleton ◽  
...  
Keyword(s):  
Articular Cartilage ◽  
Subchondral Bone ◽  
Structural Changes ◽  
Cartilage Damage ◽  
Wild Type ◽  
Significant Difference ◽  
Post Traumatic ◽  
Interleukin 15 ◽  
Joint Trauma ◽  
Surgically Induced

Post-traumatic osteoarthritis (PTOA) is a degenerative joint disease, leading to articular cartilage breakdown, osteophyte formation, and synovitis, caused by an initial joint trauma. Pro-inflammatory cytokines increase catabolic activity and may perpetuate inflammation following joint trauma. Interleukin-15 (IL-15), a pro-inflammatory cytokine, is increased in OA patients, although its roles in PTOA pathophysiology are not well characterized. Here, we utilized Il15 deficient rats to examine the role of IL-15 in PTOA pathogenesis in an injury-induced model. OA was surgically induced in Il15 deficient Holtzman Sprague-Dawley rats and control wild-type rats to compare PTOA progression. Semi-quantitative scoring of the articular cartilage, subchondral bone, osteophyte size, and synovium was performed by two blinded observers. There was no significant difference between Il15 deficient rats and wild-type rats following PTOA-induction across articular cartilage damage, subchondral bone damage, and osteophyte scoring. Similarly, synovitis scoring across six parameters found no significant difference between genetic variants. Overall, IL-15 does not appear to play a key role in the development of structural changes in this surgically-induced rat model of PTOA.

scholarly journals Arthroscopic Articular Cartilage Scores of the Canine Stifle Joint with Naturally Occurring Cranial Cruciate Ligament Disease

2020 ◽  
Author(s):  
Kimberly A. Agnello ◽  
Kei Hayashi ◽  
Dorothy Cimino Brown
Keyword(s):  
Articular Cartilage ◽  
Cruciate Ligament ◽  
Cartilage Damage ◽  
Meniscal Tear ◽  
Trochlear Groove ◽  
Cranial Cruciate Ligament ◽  
Stifle Joint ◽  
Naturally Occurring ◽  
Medial Meniscal Tear ◽  
Severity Scores

Abstract Objective This study aimed to evaluate frequency, location and severity of cartilage pathology in dogs with naturally occurring cranial cruciate ligament (CCL) disease. Study Design Stifle arthroscopic video recordings (n = 120) were reviewed. A modified Outerbridge classification system (MOCS) (0–4) was used to score cartilage at 10 locations in the femorotibial (medial and lateral femoral condyles and tibial plateaus) and patellofemoral compartments (proximal, middle and distal locations of the patella and femoral trochlear groove) of the stifle joint. Synovial pathology was scored and the presence of a medial meniscal tear was recorded. A Kruskal–Wallis test was used to evaluate association of location and synovitis with cartilage score; and presence of meniscal tear with cartilage and synovitis scores. Bonferroni correction was utilized and p < 0.05 was considered significant. Results Cartilage pathology and synovitis were identified in all joints. Overall cartilage severity scores were low (median MOCS 1). The median MOCS of the proximal trochlear groove (2) was significantly higher than all other locations evaluated. Higher synovitis scores were significantly associated with higher cartilage severity scores and a medial meniscal tear had no association with cartilage severity scores or synovitis. Conclusion Arthroscopic articular cartilage lesions are common in dogs with CCL disease at the time of surgical intervention, although the severity of cartilage damage is mild. The proximal trochlear groove of the femur had the most severe cartilage score in the stifle joint.

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.

Risk factors for progression of articular cartilage damage after anatomical anterior cruciate ligament reconstruction

2018 ◽  
Vol 100-B (3) ◽  
pp. 285-293 ◽  
Author(s):  
A. Nakamae ◽  
N. Adachi ◽  
M. Deie ◽  
M. Ishikawa ◽  
T. Nakasa ◽  
...  
Keyword(s):  
Risk Factors ◽  
Anterior Cruciate Ligament ◽  
Articular Cartilage ◽  
Acl Reconstruction ◽  
Cruciate Ligament ◽  
Cartilage Damage ◽  
Significant Risk ◽  
Articular Cartilage Damage ◽  
Anterior Cruciate

Aims To investigate the risk factors for progression of articular cartilage damage after anatomical anterior cruciate ligament (ACL) reconstruction. Patients and Methods A total of 174 patients who underwent second-look arthroscopic evaluation after anatomical ACL reconstruction were enrolled in this study. The graded condition of the articular cartilage at the time of ACL reconstruction was compared with that at second-look arthroscopy. Age, gender, body mass index (BMI), ACL reconstruction technique, meniscal conditions, and other variables were assessed by regression analysis as risk factors for progression of damage to the articular cartilage. Results In the medial compartment, multivariable logistic regression analysis indicated that partial medial meniscectomy (odds ratio (OR) 6.82, 95% confidence interval (CI) 2.11 to 22.04, p = 0.001), pivot-shift test grade at the final follow-up (OR 3.53, CI 1.39 to 8.96, p = 0.008), BMI (OR 1.15, CI 1.03 to 1.28, p = 0.015) and medial meniscal repair (OR 3.19, CI 1.24 to 8.21, p = 0.016) were significant risk factors for progression of cartilage damage. In the lateral compartment, partial lateral meniscectomy (OR 10.94, CI 4.14 to 28.92, p < 0.001) and side-to-side differences in anterior knee laxity at follow-up (OR 0.63, p = 0.001) were significant risk factors. Conclusion Partial meniscectomy was found to be strongly associated with the progression of articular cartilage damage despite r anatomical ACL reconstruction. Cite this article: Bone Joint J 2018;100-B:285–93.

Overexpression of Mig-6 in Cartilage Induces an Osteoarthritis-Like Phenotype in Mice

2020 ◽  
Author(s):  
Melina Bellini ◽  
Michael Andrew Pest ◽  
Manuela Miranda Rodrigues ◽  
Ling Qin ◽  
Jae-Wook Jeong ◽  
...  
Keyword(s):  
Bone Mineral Density ◽  
Body Composition ◽  
Articular Cartilage ◽  
Bone Mineral ◽  
Cartilage Degeneration ◽  
Negative Regulator ◽  
Control Group ◽  
Multiple Time ◽  
Mineral Density ◽  
Significant Difference

Abstract Background: Osteoarthritis (OA) is the most common form of arthritis and characterized by degeneration of articular cartilage. Mitogen-inducible gene 6 (Mig-6) has been identified as a negative regulator of the Epidermal Growth Factor Receptor (EGFR). Cartilage-specific Mig-6 knockout (KO) mice display increased EGFR signaling, an anabolic buildup of articular cartilage and formation of chondro-osseous nodules. Since our understanding of the EGFR/Mig-6 network in cartilage remains incomplete, we characterized mice with cartilage-specific overexpression of Mig-6 in this study. Methods: Utilizing knee joints from cartilage-specific Mig-6 overexpressing (Mig-6over/over) mice (at multiple time points), we evaluated the articular cartilage using histology, immunohistochemical staining and semi-quantitative histopathological scoring (OARSI) at multiple ages. MicroCT analysis was employed to examine skeletal morphometry, body composition, and bone mineral density.Results: Our data show that cartilage-specific Mig-6 overexpression did not cause any major developmental abnormalities in articular cartilage, although Mig-6over/over mice have slightly shorter long bones compared to the control group. Moreover, there was no significant difference in bone mineral density and body composition in any of the groups. However, our results indicate that Mig-6over/over male mice show accelerated cartilage degeneration at 12 and 18 months of age. Immunohistochemistry for SOX9 demonstrated that the number of positively stained cells in Mig-6over/over mice was decreased relative to controls. Immunostaining for MMP13 appeared increased in areas of cartilage degeneration in Mig-6over/over mice. Moreover, staining for phospho-EGFR (Tyr-1173) and lubricin (PRG4) was decreased in the articular cartilage of Mig-6over/over mice. Conclusion: Overexpression of Mig-6 in articular cartilage causes no major developmental phenotype; however, these mice develop earlier OA during aging. These data demonstrate that Mig-6/EGFR pathways is critical for joint homeostasis and might present a promising therapeutic target for OA.

Sign in / Sign up

Export Citation Format

Share Document