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 ◽  
...  

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.

2021 ◽  
Vol 11 (15) ◽  
pp. 7118
Author(s):  
Ermina Hadzic ◽  
Garth Blackler ◽  
Holly Dupuis ◽  
Stephen James Renaud ◽  
Christopher Thomas Appleton ◽  
...  

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.


2021 ◽  
Vol 14 (2) ◽  
pp. 188-192
Author(s):  
Ewa Walewska

Osteoarthritis, which affects approximately 18% of women and 10% of men after the age of 60, is undoubtedly a serious public problem. The main pathological changes in osteoarthritis include the degeneration and loss of articular cartilage, changes in the subchondral bone and osteophyte formation in the bone epiphyses. Pain accompanying degenerative modifications significantly reduces the quality of life of patients. The purpose of this article is to discuss the use of unsaponifiable fractions of avocado and soybean oil to control the symptoms of osteoarthritis of the knee on a case-by-case basis.


2019 ◽  
Vol 4 (6) ◽  
pp. 221-229 ◽  
Author(s):  
Simon Donell

Subchondral bone remodelling is an integral part of osteoarthritis and involves the development of subchondral sclerosis seen on plain imaging, along with osteophyte formation. The development of these changes is due to persistent abnormal mechanical stresses which create a cellular and biomolecular response to microfractures in the subchondral bone and osteochondral junction. An early sign is bone marrow lesions seen on MRI scanning. Healing can occur at this stage by correcting the abnormal loads. Persistence leads to what is thought to be a delayed union or nonunion response by the bone. Microfractures of the osteochondral junction, coupled with articular cartilage fissuring and loss, allows synovial fluid to penetrate the subchondral bone along with cytokines and other molecules reacting with the bone cells to increase the pathological effects. This review gives an overview of the current thoughts on subchondral bone remodelling in osteoarthritis that is aimed at orthopaedic surgeons to help in the understanding of the pathogenesis of osteoarthritis and the role of surgical management. Cite this article: EFORT Open Rev 2019;4 DOI: 10.1302/2058-5241.4.180102


2017 ◽  
Vol 300 (7) ◽  
pp. 1208-1218 ◽  
Author(s):  
Paolo Baudi ◽  
Fabio Catani ◽  
Manuela Rebuzzi ◽  
Marzia Ferretti ◽  
Alberto Smargiassi ◽  
...  

2020 ◽  
Vol 10 (23) ◽  
pp. 8673 ◽  
Author(s):  
Johannes Pordzik ◽  
Anke Bernstein ◽  
Julius Watrinet ◽  
Hermann O. Mayr ◽  
Sergio H. Latorre ◽  
...  

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.


Cells ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 1462
Author(s):  
Aimy Sebastian ◽  
Jillian L. McCool ◽  
Nicholas R. Hum ◽  
Deepa K. Murugesh ◽  
Stephen P. Wilson ◽  
...  

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.


Pharmaceutics ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 1503
Author(s):  
Marcus Deloney ◽  
Parssa Garoosi ◽  
Vanessa F. C. Dartora ◽  
Blaine A. Christiansen ◽  
Alyssa Panitch

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.


Cartilage ◽  
2021 ◽  
pp. 194760352110605
Author(s):  
M.P.F. Janssen ◽  
M.J.M. Peters ◽  
E.G.M. Steijvers-Peeters ◽  
P. Szomolanyi ◽  
E.M.C. Jutten ◽  
...  

Objective To evaluate the morphological and biochemical quality of cartilage transplants and surrounding articular cartilage of patients 25 years after perichondrium transplantation (PT) and autologous chondrocyte transplantation (ACT) as measured by ultra-high-field 7-Tesla (7T) magnetic resonance imaging (MRI) and to present these findings next to clinical outcome. Design Seven PT patients and 5 ACT patients who underwent surgery on the femoral condyle between 1986 and 1996 were included. Patient-reported outcome measures (PROMs) were assessed by the clinical questionnaires: Knee injury and Osteoarthritis Outcome Score (KOOS), International Knee Documentation Committee (IKDC), and Visual Analogue Scale (VAS) for knee pain. The morphological (MOCART score) and biochemical quality (glycosaminoglycans [GAGs] content and collagen integrity) of cartilage transplants and surrounding articular cartilage were analyzed by 7T MRI. The results of the PT and ACT patients were compared. Finally, a detailed morphological analysis of the grafts alone was performed. Results No statistically significant difference was found for the PROMs and MOCART scores of PT and ACT patients. Evaluation of the graft alone showed poor repair tissue quality and high prevalence of intralesional osteophyte formation in both the PT and ACT patients. Penetration of the graft surface by the intralesional osteophyte was related to biochemically damaged opposing tibial cartilage; GAG content was significantly lower in patients with an osteophyte penetrating the graft surface. Conclusions Both PT and ACT patients have a high incidence of intralesional osteophyte formation 25 years after surgery. The resulting biochemical damage to the opposing tibial cartilage might be dependent on osteophyte morphology.


PLoS ONE ◽  
2021 ◽  
Vol 16 (7) ◽  
pp. e0254383
Author(s):  
Ikufumi Takahashi ◽  
Keisuke Takeda ◽  
Taro Matsuzaki ◽  
Hiroshi Kuroki ◽  
Masahiro Hoso

The purpose of this study was to clarify the histological effect of reducing the loading to knee on cartilage degeneration, osteophyte formation, and synovitis in early-stage osteoarthritis (OA) using a post-traumatic rat model. Ten male rats were randomly allocated into two experimental groups: OA induction by surgical destabilization of medial meniscus (DMM, OA group) and hindlimb suspension after OA induction by DMM (OAHS group). The articular cartilage, osteophyte formation, and synovial membrane in the medial tibiofemoral joint were analyzed histologically and histomorphometrically at 2 and 4 weeks after surgery. The histological scores and changes in articular cartilage and osteophyte formation were significantly milder and slower in the OAHS group than in the OA group. At 2 and 4 weeks, there were no significant differences in cartilage thickness and matrix staining intensity between both the groups, but chondrocytes density was significantly lower in the OA group. Synovitis was milder in OAHS group than in OA group at 2 weeks. Reducing knee joint loading inhibited histological OA changes in articular cartilage, osteophyte formation, and synovial inflammation. This result supports the latest clinical guidelines for OA treatment. Further studies using biochemical and mechanical analyses are necessary to elucidate the mechanism underlying delayed OA progression caused by joint-load reduction.


2021 ◽  
Vol 42 ◽  
pp. 179-195
Author(s):  
N Angrisani ◽  
◽  
R Willumeit-Römer ◽  
H Windhagen ◽  
B Mavila Chathoth ◽  
...  

No optimal therapy exists to stop or cure chondral degeneration in osteoarthritis (OA). While the pathogenesis is unclear, there is consensus on the etiological involvement of both articular cartilage and subchondral bone. Compared to original bone, the substance of sclerotic bone is mechanically less solid. The osteoproliferative effect of Mg has been shown repeatedly during development of Mg-based osteosynthesis implants. The aim of the present study was to examine the influence of implanted high-purity Mg cylinders on subchondral bone quality in a rabbit OA model. 10 New Zealand White rabbits received into the knee either 20 empty drill holes or 20 drill holes, which were additionally filled with one Mg cylinder each. Follow-up was at 8 weeks. Micro-computed tomography (µCT) was performed. After euthanasia, cartilage condition was determined, bone samples were collected and processed for histological evaluation and elemental imaging by micro-X-ray fluorescence spectrometry (µXRF). Articular cartilage collected post-mortem showed different stages of lesions, from mild alterations up to exposed subchondral bone, which tended to be slightly lower in animals with implanted Mg cylinders. µCT showed significantly increased bone volume in the Mg group. Also, histological evaluation revealed distinct differences. While right, operated limbs did not show any significant difference, left, non-operated controls showed significantly less changes in articular cartilage in the Mg group. A distinct influence of implanted cylinders of pure Mg on subchondral bone of osteoarthritic rabbits was shown. Subsequent evaluations, including other time points and alternative alloys, will show if this could alter OA progression.


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