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 Genetic deletion of interleukin-15 is not associated with major structural changes following experimental post-traumatic knee osteoarthritis in rats

2021 ◽  
Author(s):  
Ermina Hadzic ◽  
Garth Blackler ◽  
Holly Dupuis ◽  
Stephen J Renaud ◽  
C. Thomas Appleton ◽  
...  
Keyword(s):  
Articular Cartilage ◽  
Subchondral Bone ◽  
Structural Changes ◽  
Wild Type ◽  
Osteophyte Formation ◽  
Significant Difference ◽  
Post Traumatic ◽  
Interleukin 15 ◽  
Joint Trauma ◽  
Surgically Induced

AbstractPost-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 OA pathophysiology are not well characterized.IL-15 levels appear to correlate to self-reported pain levels, and polymorphisms in the IL-15 receptor alpha gene correlate to a 1.5-fold increase in OA symptoms. This could be due to IL-15 effects on the activity of proteinases, such as matrix metalloproteinases (MMP) −1, −3, and −7. Here we utilized Il15 deficient rats to examine the role of IL-15 in PTOA pathogenesis in an injury-induced model of OA. OA was surgically induced in Il15 deficient 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. Analyses of articular cartilage damage, subchondral bone damage, and osteophyte formation revealed no significant difference between Il15 deficient rats and wild-type rats following PTOA-induction. Similarly, synovitis scoring across 6 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 Morphological Study: Ultrastructural Aspects of Articular Cartilage and Subchondral Bone in Patients Affected by Post-Traumatic Shoulder Instability

2017 ◽  
Vol 300 (7) ◽  
pp. 1208-1218 ◽  
Author(s):  
Paolo Baudi ◽  
Fabio Catani ◽  
Manuela Rebuzzi ◽  
Marzia Ferretti ◽  
Alberto Smargiassi ◽  
...  
Keyword(s):  
Articular Cartilage ◽  
Subchondral Bone ◽  
Shoulder Instability ◽  
Morphological Study ◽  
Post Traumatic

Proteinase-activated Receptor-2 Gene Disruption Limits the Effect of Osteoarthritis on Cartilage in Mice: A Novel Target in Joint Degradation

2011 ◽  
Vol 38 (5) ◽  
pp. 911-920 ◽  
Author(s):  
NATHALIE AMIABLE ◽  
JOHANNE MARTEL-PELLETIER ◽  
BERTRAND LUSSIER ◽  
STEEVE KWAN TAT ◽  
JEAN-PIERRE PELLETIER ◽  
...  
Keyword(s):  
Subchondral Bone ◽  
Structural Changes ◽  
Therapeutic Potential ◽  
Cartilage Damage ◽  
Bone Surface ◽  
Trabecular Thickness ◽  
Post Surgery ◽  
Novel Target ◽  
The Right

Objective.Evidence indicates that proteinase-activated receptor (PAR)-2 participates in the degradative processes of human osteoarthritis (OA). We evaluated the in vivo effect of PAR-2 on articular lesions in a PAR-2-knockout (KO) mouse model of OA.Methods.OA was surgically induced by destabilization of the medial meniscus of the right knee in C57Bl/6 wild-type (WT) and PAR-2 KO mice. Knee swelling was measured throughout the duration of the study (8 weeks postsurgery) and histologic evaluation of cartilage was done to assess structure, cellularity, matrix staining, and remodeling in the deep zone. Morphometric analysis of subchondral bone was also performed.Results.Data showed significant knee swelling in the operated WT mice immediately following surgery, which increased with time (8 weeks post-surgery). Knee swelling was significantly lower (p ≤ 0.0001) in PAR-2 KO mice than in WT mice at both 4 and 8 weeks postsurgery. Cartilage damage was found in both operated WT and PAR-2 KO mice; however, lesions were significantly less severe (global score; p ≤ 0.05) in the PAR-2 KO mice at 4 weeks postsurgery. Operated WT mice showed reduced subchondral bone surface and trabecular thickness with significance reached at 4 weeks (p ≤ 0.03 and p ≤ 0.05, respectively), while PAR-2 KO mice demonstrated a gradual increase in subchondral bone surface with significance reached at 8 weeks (p ≤ 0.007).Conclusion.We demonstrated the in vivo implication of PAR-2 in the development of experimental OA, thus confirming its involvement in OA joint structural changes and reinforcing the therapeutic potential of a PAR-2 antagonist for treatment of OA.

scholarly journals Correlation of Biomechanical Alterations under Gonarthritis between Overlying Menisci and Articular Cartilage

2020 ◽  
Vol 10 (23) ◽  
pp. 8673 ◽  
Author(s):  
Johannes Pordzik ◽  
Anke Bernstein ◽  
Julius Watrinet ◽  
Hermann O. Mayr ◽  
Sergio H. Latorre ◽  
...  
Keyword(s):  
Articular Cartilage ◽  
Applied Load ◽  
Structural Changes ◽  
Tibial Plateau ◽  
Biomechanical Properties ◽  
Posterior Horn ◽  
Joint Surfaces ◽  
Significant Difference ◽  
Instantaneous Modulus ◽  
Biomechanical Changes

Just like menisci, articular cartilage is exposed to constant and varying stresses. Injuries to the meniscus are associated with the development of gonarthritis. Both the articular cartilage and the menisci are subject to structural changes under gonarthritis. The aim of this study was to investigate biomechanical alterations in articular cartilage and the menisci under gonarthritis by applying an indentation method. The study assessed 11 menisci from body donors as controls and 21 menisci from patients with severe gonarthritis. For the simultaneous examination of the articular cartilage and the menisci, we only tested the joint surfaces of the tibial plateau covered by the corresponding menisci. Over the posterior horn of the meniscus, the maximum applied load—the highest load registered by the load cell—of the arthritic samples of 0.02 ± 0.02 N was significantly greater (p = 0.04) than the maximum applied load of the arthritis-free samples of 0.01 ± 0.01 N. The instantaneous modulus (IM) at the center of the arthritic cartilage covered by the meniscus with 3.5 ± 2.02 MPa was significantly smaller than the IM of the arthritis-free samples with 5.17 ± 1.88 MPa (p = 0.04). No significant difference was found in the thickness of the meniscus-covered articular cartilage between the arthritic and arthritis-free samples. Significant correlations between the articular cartilage and the corresponding menisci were not observed at any point. In this study, the biomechanical changes associated with gonarthritis affected the posterior horn of the meniscus and the mid region of the meniscus-covered articular cartilage. The assessment of cartilage thickness as a structural characteristic of osteoarthritis may be misleading with regard to the interpretation of articular cartilage’s biomechanical properties.

scholarly journals Single-Cell RNA-Seq Reveals Transcriptomic Heterogeneity and Post-Traumatic Osteoarthritis-Associated Early Molecular Changes in Mouse Articular Chondrocytes

Cells ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 1462
Author(s):  
Aimy Sebastian ◽  
Jillian L. McCool ◽  
Nicholas R. Hum ◽  
Deepa K. Murugesh ◽  
Stephen P. Wilson ◽  
...  
Keyword(s):  
Articular Cartilage ◽  
Single Cell ◽  
Articular Chondrocytes ◽  
Cartilage Degeneration ◽  
Cell Types ◽  
Knee Joints ◽  
Molecular Changes ◽  
Post Traumatic ◽  
Joint Trauma ◽  
Functional Profiles

Articular cartilage is a connective tissue lining the surfaces of synovial joints. When the cartilage severely wears down, it leads to osteoarthritis (OA), a debilitating disease that affects millions of people globally. The articular cartilage is composed of a dense extracellular matrix (ECM) with a sparse distribution of chondrocytes with varying morphology and potentially different functions. Elucidating the molecular and functional profiles of various chondrocyte subtypes and understanding the interplay between these chondrocyte subtypes and other cell types in the joint will greatly expand our understanding of joint biology and OA pathology. Although recent advances in high-throughput OMICS technologies have enabled molecular-level characterization of tissues and organs at an unprecedented resolution, thorough molecular profiling of articular chondrocytes has not yet been undertaken, which may be in part due to the technical difficulties in isolating chondrocytes from dense cartilage ECM. In this study, we profiled articular cartilage from healthy and injured mouse knee joints at a single-cell resolution and identified nine chondrocyte subtypes with distinct molecular profiles and injury-induced early molecular changes in these chondrocytes. We also compared mouse chondrocyte subpopulations to human chondrocytes and evaluated the extent of molecular similarity between mice and humans. This work expands our view of chondrocyte heterogeneity and rapid molecular changes in chondrocyte populations in response to joint trauma and highlights potential mechanisms that trigger cartilage degeneration.

scholarly journals Hyaluronic Acid-Binding, Anionic, Nanoparticles Inhibit ECM Degradation and Restore Compressive Stiffness in Aggrecan-Depleted Articular Cartilage Explants

Pharmaceutics ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 1503
Author(s):  
Marcus Deloney ◽  
Parssa Garoosi ◽  
Vanessa F. C. Dartora ◽  
Blaine A. Christiansen ◽  
Alyssa Panitch
Keyword(s):  
Hyaluronic Acid ◽  
Articular Cartilage ◽  
Cartilage Explants ◽  
Inflammatory Cytokine Production ◽  
Compressive Stiffness ◽  
Ecm Degradation ◽  
Post Traumatic ◽  
Joint Trauma ◽  
Localized Treatment ◽  
Hyaluronic Acid Binding

Joint trauma results in the production of inflammatory cytokines that stimulate the secretion of catabolic enzymes, which degrade articular cartilage. Molecular fragments of the degraded articular cartilage further stimulate inflammatory cytokine production, with this process eventually resulting in post-traumatic osteoarthritis (PTOA). The loss of matrix component aggrecan occurs early in the progression of PTOA and results in the loss of compressive stiffness in articular cartilage. Aggrecan is highly sulfated, associates with hyaluronic acid (HA), and supports the compressive stiffness in cartilage. Presented here, we conjugated the HA-binding peptide GAHWQFNALTVRGSG (GAH) to anionic nanoparticles (hNPs). Nanoparticles conjugated with roughly 19 GAH peptides, termed 19 GAH-hNP, bound to HA in solution and increased the dynamic viscosity by 94.1% compared to an HA solution treated with unconjugated hNPs. Moreover, treating aggrecan-depleted (AD) cartilage explants with 0.10 mg of 19 GAH-hNP restored the cartilage compressive stiffness to healthy levels six days after a single nanoparticle treatment. Treatment of AD cartilage with 0.10 mg of 19 GAH-hNP inhibited the degradation of articular cartilage. Treated AD cartilage had 409% more collagen type II and 598% more GAG content than untreated-AD explants. The 19 GAH-hNP therapeutic slowed ECM degradation in AD cartilage explants, restored the compressive stiffness of damaged cartilage, and showed promise as a localized treatment for PTOA.

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 Regional Genetic Responses of Porcine Talar Articular Cartilage to Impact Injury

2019 ◽  
Vol 4 (4) ◽  
pp. 2473011419S0012
Author(s):  
Evan (Hank) Bryant ◽  
Kailey Mansour ◽  
C.Y. Charles Huang ◽  
Jonathan R. Kaplan ◽  
Amiethab A. Aiyer
Keyword(s):  
Articular Cartilage ◽  
Ex Vivo ◽  
Cartilage Damage ◽  
Rna Extraction ◽  
Posterior Region ◽  
Anterior Region ◽  
Inferior Aspect ◽  
Catabolic Genes ◽  
Post Traumatic ◽  
Impact Injury

Category: Ankle Arthritis Introduction/Purpose: The ankle is at greatest risk for post-traumatic osteoarthritis (PTOA) in comparison to the hip or knee. Adaptive changes to the cartilaginous topography may be a marker for where cartilage damage poses the greatest risk of development of osteoarthritis. The objective of this study was to elucidate the mechanism of PTOA by analyzing the changes in regional genetic expression of inflammatory markers after impact injury in an ex-vivo porcine model. Methods: Talus bones were recovered from 5 porcine ankles. A drop tower was used to induce injury by dropping a 1000 g weight from a height of 15 cm on the talus. Following the injury the bone was cultured for 24 hours. Four 6-mm cartilage plugs were harvested from the inferior aspect of each talus bone and a small slice of each plug was used for cell imaging. The remaining cartilage plugs were flash frozen with liquid nitrogen and stored at -80°C for ribonucleic acid (RNA) extraction and analysis of gene expression. Expression of inflammatory and catabolic genes (IL1-ß, TNF-a, ADAMTS-5, ADAMTS-4, MMP-3 and MMP-13) was compared among the samples obtained from the non-impacted and impacted sites of the anterior and posterior regions. Student t-test was performed to examine the differences between the control (non-impact) and impacted samples from each region and between the control samples from the anterior and posterior regions. Results: The current porcine impact model demonstrated significant up-regulation of several inflammatory cytokines and metalloproteinases by impact force. Among the genes tested, TNF-a, ADAMTS-4, and MMP-3 showed increased expression at impact sites (p<0.05) compared to non-impact sites in the posterior region (Figure 1) whereas no differences were found in the anterior region. Interestingly, the non-impacted samples in the anterior region exhibited significantly higher expression of TNF-a, ADAMTS-4, MMP-3 and ADAMTS-5 than those of the posterior region (p<0.05). Conclusion: The results of the current ex-vivo porcine impact study demonstrate significant up-regulation of inflammatory and catabolic genes 24 hours after porcine talus bone impaction. These findings highlight the relevance of regional differences in post- traumatic ankle inflammation; the posterior region of porcine talar articular cartilage demonstrated increased sensitivity in response to injury. The anterior region illustrated greater resistance to injury, showing less gene up-regulation compared to the posterior region of the same ankle. These findings suggest that location of cartilage injury may play a crucial role in the development of inflammatory response, chondrocyte apoptosis, and subsequent osteoarthritis of the ankle.

Topographic modeling of early human osteoarthritis in sheep

2019 ◽  
Vol 11 (508) ◽  
pp. eaax6775 ◽  
Author(s):  
Tamás Oláh ◽  
Jan Reinhard ◽  
Liang Gao ◽  
Sophie Haberkamp ◽  
Lars K. H. Goebel ◽  
...  
Keyword(s):  
Subchondral Bone ◽  
Cartilage Damage ◽  
Spatiotemporal Data ◽  
Translational Model ◽  
Knee Oa ◽  
Regenerative Therapies ◽  
Surgically Induced ◽  
Early Oa ◽  
Osteochondral Unit ◽  
Early Human

Articular cartilage damage occurring during early osteoarthritis (OA) is a key event marking the development of the disease. Here, we modeled early human OA by gathering detailed spatiotemporal data from surgically induced knee OA development in sheep. We identified a specific topographical pattern of osteochondral changes instructed by a defined meniscal injury, showing that both cartilage and subchondral bone degeneration are initiated from the region adjacent to the damage. Alterations of the subarticular spongiosa arising locally and progressing globally disturbed the correlations of cartilage with subchondral bone seen at homeostasis and were indicative of disease progression. We validated our quantitative findings against human OA, showing a similar pattern of early OA correlating with regions of meniscal loss and an analogous late critical disturbance within the entire osteochondral unit. This translational model system can be used to elucidate mechanisms of OA development and provides a roadmap for investigating regenerative therapies.

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