scholarly journals Males and Females Have Distinct Molecular Events in the Articular Cartilage During Knee Osteoarthritis

2021 ◽  
Vol 22 (15) ◽  
pp. 7876
Author(s):  
Chenshuang Li ◽  
Zhong Zheng
Keyword(s):  
Articular Cartilage ◽  
Fibrin Clot ◽  
Molecular Events ◽  
Healthy Cartilage ◽  
Differential Expression Genes ◽  
Healthy Female ◽  
Public Health Challenge ◽  
Males And Females ◽  
Transcriptomic Level ◽  
Plug Formation

Osteoarthritis (OA) is a major public health challenge that imposes a remarkable burden on the affected individuals and the healthcare system. Based on the clinical observation, males and females have different prevalence rates and severity levels of OA. Thus, sex-based differences may play essential roles in OA’s prognosis and treatment outcomes. To date, the comprehensive understanding of the relationship between sex and OA is still largely lacking. In the current study, we analyzed a published transcriptome dataset of knee articular cartilage (GSE114007) from 18 healthy (five females, 13 males) and 20 OA (11 females, nine males) donors to provide a slight insight into this important but complex issue. First, comparing female healthy cartilage samples with those of males revealed 36 differential expression genes (DEGs), indicating the fundamental sex-related differences at the molecular level. Meanwhile, 923 DEGs were distinguished between OA and healthy female cartilage, which can be enriched to 15 Reactome pathways. On the other hand, when comparing OA and healthy male cartilage, there are only 419 DEGs were identified, and only six pathways were enriched against the Reactome database. The different signaling response to OA in the male and female cartilage was further enforced by recognizing 50 genes with significantly different OA-responsive expression fold changes in males and females. Particularly, 14 Reactome pathways, such as “Extracellular matrix organization”, “Collagen biosynthesis and modifying enzymes”, “Dissolution of fibrin clot”, and “Platelet Aggregation (Plug formation)”, can be noted from these 50 sex-dependent OA-responsive genes. Overall, the current study explores the Sex as a Biological Variable (SABV) at the transcriptomic level in the knee articular cartilage in both healthy status and OA event, which could help predict the differential OA prognosis and treatment outcome of males and female patients.

Coagulation (Hemostasis and Thrombosis)

2012 ◽  
Author(s):  
Rajiv K. Pruthi
Keyword(s):  
Risk Factors ◽  
Platelet Activation ◽  
Coagulation Factors ◽  
Fibrin Clot ◽  
Coagulation System ◽  
Bleeding Disorders ◽  
Hemostatic System ◽  
Blood Clots ◽  
Anticoagulant System ◽  
Plug Formation

The coagulation system has 2 essential functions: to maintain hemostasis and to prevent and limit thrombosis. The procoagulant component of the hemostatic system prevents and controls hemorrhage. Vascular injury results in activation of hemostasis, which consists of vasospasm, platelet plug formation (platelet activation, adhesion, and aggregation), and fibrin clot formation (by activation of coagulation factors in the procoagulant system). The anticoagulant system prevents excessive formation of blood clots, and the fibrinolytic system breaks down and remodels blood clots. Quantitative abnormalities (deficiencies) and qualitative abnormalities of platelets and coagulation factors lead to bleeding disorders, whereas deficiencies of the anticoagulant system are risk factors for thrombosis. Common disorders of hemostasis and thrombosis are reviewed.

The Effect of Articular Cartilage Focal Defect Size and Location in Whole Knee Biomechanics Models

2019 ◽  
Vol 142 (2) ◽  
Author(s):  
Benjamin C. Marchi ◽  
Ellen M. Arruda ◽  
Rhima M. Coleman
Keyword(s):  
Articular Cartilage ◽  
Soft Tissue Injuries ◽  
Joint Kinematics ◽  
Tissue Deformation ◽  
Tibial Cartilage ◽  
Cartilage Mechanics ◽  
Articular Surfaces ◽  
Healthy Cartilage ◽  
Spatial Locations ◽  
Global Reduction

Abstract Articular cartilage focal defects are common soft tissue injuries potentially linked to osteoarthritis (OA) development. Although several defect characteristics likely contribute to osteoarthritis, their relationship to local tissue deformation remains unclear. Using finite element models with various femoral cartilage geometries, we explore how defects change cartilage deformation and joint kinematics assuming loading representative of the maximum joint compression during the stance phase of gait. We show how defects, in combination with location-dependent cartilage mechanics, alter deformation in affected and opposing cartilages, as well as joint kinematics. Small and average sized defects increased maximum compressive strains by approximately 50% and 100%, respectively, compared to healthy cartilage. Shifts in the spatial locations of maximum compressive strains of defect containing models were also observed, resulting in loading of cartilage regions with reduced initial stiffnesses supporting the new, elevated loading environments. Simulated osteoarthritis (modeled as a global reduction in mean cartilage stiffness) did not significantly alter joint kinematics, but exacerbated tissue deformation. Femoral defects were also found to affect healthy tibial cartilage deformations. Lateral femoral defects increased tibial cartilage maximum compressive strains by 25%, while small and average sized medial defects exhibited decreases of 6% and 15%, respectively, compared to healthy cartilage. Femoral defects also affected the spatial distributions of deformation across the articular surfaces. These deviations are especially meaningful in the context of cartilage with location-dependent mechanics, leading to increases in peak contact stresses supported by the cartilage of between 11% and 34% over healthy cartilage.

A CURRENT REVIEW ON THE BIOLOGY AND TREATMENT OF ARTICULAR CARTILAGE DEFECTS (PART I & PART II)

2003 ◽  
Vol 07 (03n04) ◽  
pp. 157-181 ◽  
Author(s):  
Craig Willers ◽  
David J. Wood ◽  
Ming H. Zheng
Keyword(s):  
Articular Cartilage ◽  
Subchondral Bone ◽  
18Th Century ◽  
Later Life ◽  
Fibrin Clot ◽  
Joint Disease ◽  
Cartilage Defects ◽  
Adult Males ◽  
Chondrocyte Implantation ◽  
Osteochondral Injury

Osteochondral injury occurs predominantly in physically active young adult males. Injury to the articular cartilage and/or subchondral bone may not only cause acute joint disease resulting in osseous intracapsular (synovitis) or extracapsular pain, but may also act to spawn arthritic conditions in later life. Since the 18th century, such injury has proven difficult to treat clinically, and much therapy has been essentially palliative. Past treatments such as abrasion arthroplasty, drilling, microfracture and arthroscopic lavage have been useful in removing articular debris and promoting the formation of the fibrin clot used in most native repair mechanisms. However, the limitation of these techniques is their inability to restore the damaged cartilage and subchondral bone to their normal tissue architecture. Recent developments in tissue engineering have concentrated on the utilization of autologous chondrocyte implantation, biomaterials and growth factors to promote the regeneration of biomechanically superior hyaline articular cartilage. This paper reviews the etiology, repair biology and therapeutic techniques of cartilage and/or osteochondral injury over the previous decades, and attempts to provide insight into interesting new research directions which offer much potential for improved treatment of these troublesome lesions.

scholarly journals Integrated analysis of ischemic stroke datasets revealed sex and age difference in anti-stroke targets

PeerJ ◽  
2016 ◽  
Vol 4 ◽  
pp. e2470 ◽  
Author(s):  
Wen-Xing Li ◽  
Shao-Xing Dai ◽  
Qian Wang ◽  
Yi-Cheng Guo ◽  
Yi Hong ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Target Genes ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Integrated Analysis ◽  
Age Difference ◽  
Differential Expression Genes ◽  
Males And Females ◽  
Young Subjects ◽  
Microarray Datasets

Ischemic stroke is a common neurological disorder and the burden in the world is growing. This study aims to explore the effect of sex and age difference on ischemic stroke using integrated microarray datasets. The results showed a dramatic difference in whole gene expression profiles and influenced pathways between males and females, and also in the old and young individuals. Furthermore, compared with old males, old female patients showed more serious biological function damage. However, females showed less affected pathways than males in young subjects. Functional interaction networks showed these differential expression genes were mostly related to immune and inflammation-related functions. In addition, we found ARG1 and MMP9 were up-regulated in total and all subgroups. Importantly, IL1A, ILAB, IL6 and TNF and other anti-stroke target genes were up-regulated in males. However, these anti-stroke target genes showed low expression in females. This study found huge sex and age differences in ischemic stroke especially the opposite expression of anti-stroke target genes. Future studies are needed to uncover these pathological mechanisms, and to take appropriate pre-prevention, treatment and rehabilitation measures.

scholarly journals Cryopreserved, Thin, Laser-Etched Osteochondral Allograft Maintains the Functional Components of Articular Cartilage After Two Years of Storage

2020 ◽  
Author(s):  
Carolyn B Rorick ◽  
Jordyn A Mitchell ◽  
Ruth H Bledsoe ◽  
Michael L Floren ◽  
Ross M Wilkins
Keyword(s):  
Flow Cytometry ◽  
Articular Cartilage ◽  
Growth Factor ◽  
Treatment Options ◽  
Osteochondral Allograft ◽  
Protein Signaling ◽  
Chondral Defects ◽  
Healthy Cartilage ◽  
Functional Components

Abstract Background : Despite improvements in treatment options and techniques, articular cartilage repair continues to be a challenge for orthopedic surgeons. This study provides data to support that the 2-year Cryopreserved, Thin, Laser-Etched Osteochondral Allograft (T-LE Allograft) embodies the necessary viable cells, protein signaling, and extracellular matrix (ECM) scaffold found in fresh cartilage in order to facilitate a positive clinical outcome for cartilage defect replacement and repair. Methods: Viability testing was performed by digestion of the graft, cells were counted using a trypan blue assay. Growth factor and ECM protein content was quantified using biochemical assays. A fixation model was introduced to assess tissue outgrowth capability and cellular metabolic activity in vitro . Histological and immunofluorescence staining were employed to confirm tissue architecture, cellular outgrowth, and presence of ECM. The effects of the T-LE Allograft to signal bone marrow-derived mesenchymal stem cell (BM-MSC) migration and chondrogenic differentiation were evaluated using in vitro co-culture assays. Immunogenicity testing was completed using flow cytometry analysis of cells obtained from digested T-LE Allografts and fresh articular cartilage. Results: Average viability of the T-LE Allograft post-thaw was found to be 94.97 ±3.38%, compared to 98.83 ±0.43% for fresh articular cartilage. Explant studies from the in vitro fixation model confirmed the long-term viability and proliferative capacity of these chondrocytes. Growth factor and ECM proteins were quantified for the T-LE Allograft revealing similar profiles to fresh articular cartilage. Cellular signaling of the T-LE Allograft and fresh articular cartilage both exhibited similar outcomes in co-culture for migration and differentiation of BM-MSCs. Flow cytometry testing confirmed the T-LE Allograft is immune-privileged as it is negative for immunogenic markers and positive for chondrogenic markers. Conclusions: Using our novel, proprietary cryopreservation method, the T-LE Allograft retains excellent cellular viability, with native-like growth factor and ECM composition of healthy cartilage after two years of storage at -80 o C. The successful cryopreservation of the T-LE Allograft alleviates the limited availably of conventionally used fresh osteochondral allograft (OCA), by providing a readily available and simple to use allograft solution. The results presented in this paper supports clinical data that the T-LE Allograft can be a successful option for repairing chondral defects.

scholarly journals Functional roles of COMP and TSP-4 in articular cartilage and their relevance in osteoarthritis

2021 ◽  
Author(s):  
◽  
Kathrin Maly
Keyword(s):  
Gene Expression ◽  
Articular Cartilage ◽  
Protein Level ◽  
Functional Role ◽  
Human Articular Cartilage ◽  
Serum Samples ◽  
Superficial Zone ◽  
Ecm Proteins ◽  
Healthy Cartilage

Osteoarthritis (OA) is a slowly progressing disease, resulting in the degradation of cartilage and the loss of joint functionality. The cartilage extracellular matrix (ECM) is degraded and undergoes remodelling in OA progression. Chondrocytes start to express degrading proteases but are also reactivated and synthesise ECM proteins. The spectrum of these newly synthesised proteins and their involvement in OA specific processes and cartilage repair is hardly investigated. Human articular cartilage obtained from OA patients undergoing knee replacement surgery was evaluated according to the OARSI histopathology grading system. Healthy, non-OA cartilage samples were used as controls. The expression and distribution of thrombospondin-4 (TSP-4) and the closely related COMP were analysed on the gene level by PCR and on the protein level by immunohistology and immunoblot assays. The potential of TSP-4 as a diagnostic marker was evaluated by immunoblot assays, using serum samples from OA patients and healthy individuals. The functional role of both proteins was further investigated in in vitro studies using chondrocytes isolated from femoral condyles of healthy pigs. The effect of COMP and TSP-4 on chondrocyte migration and attachment was investigated via transwell and attachment assays, respectively. Moreover, the potential of COMP and TSP-4 to modulate the chondrocyte phenotype by inducing gene expression, ECM protein synthesis and matrix formation was investigated by immunofluorescence staining and qPCR. The activation of cartilage relevant signalling pathways was investigated by immunoblot assays. These results showed for the first time the presence of TSP-4 in articular cartilage. Its amount dramatically increased in OA compared to healthy cartilage and correlated positively with OA severity. In healthy cartilage TSP-4 was primarily found in the superficial zone while it was wider distributed in the middle and deeper zones of OA cartilage. The amount of specific TSP-4 fragments was increased in sera of OA patients compared to healthy controls, indicating a potential to serve as an OA biomarker. COMP was ubiquitously expressed in healthy cartilage but degraded in early as well as re-expressed in late-stage OA. The overall protein levels between OA severity grades were comparable. Contrary to TSP-4, COMP was localised primarily in the upper zone of OA cartilage, in particular in areas with severe damage. COMP could attract chondrocytes and facilitated their attachment, while TSP-4 did not affect these processes. COMP and TSP 4 were generally weak inducers of gene expression, although both could induce COL2A1 and TSP-4 additionally COL12A1 and ACAN after 6 h. Correlating data were obtained on the protein level: COMP and TSP-4 promoted the synthesis and matrix formation of collagen II, collagen IX, collagen XII and proteoglycans. In parallel, both proteins suppressed chondrocyte hypertrophy and dedifferentiation by reducing collagen X and collagen I. By analysing the effect of COMP and TSP-4 on intracellular signalling, both proteins induced Erk1/2 phosphorylation and TSP-4 could further promote Smad2/3 signalling induced by TGF-β1. None of the two proteins had a direct or modulatory effect on Smad1/5/9 dependent signalling. In summary, COMP and TSP-4 contribute to ECM maintenance and repair by inducing the expression of essential ECM proteins and suppressing chondrocyte dedifferentiation. These effects might be mediated by Erk1/2 phosphorylation. The presented data demonstrate an important functional role of COMP and TSP-4 in both healthy and OA cartilage and provide a basis for further studies on their potential in clinical applications for OA diagnosis and treatment.

scholarly journals Cryopreserved, Thin, Laser-Etched Osteochondral Allograft Maintains the Functional Components of Articular Cartilage After Two Years of Storage

2020 ◽  
Author(s):  
Carolyn B Rorick ◽  
Jordyn A Mitchell ◽  
Ruth H Bledsoe ◽  
Michael L Floren ◽  
Ross M Wilkins
Keyword(s):  
Flow Cytometry ◽  
Articular Cartilage ◽  
Growth Factor ◽  
Treatment Options ◽  
Osteochondral Allograft ◽  
Protein Signaling ◽  
Chondral Defects ◽  
Healthy Cartilage ◽  
Functional Components

Abstract Background : Despite improvements in treatment options and techniques, articular cartilage repair continues to be a challenge for orthopedic surgeons. This study provides data to support that the 2-year Cryopreserved, Thin, Laser-Etched Osteochondral Allograft (T-LE Allograft) embodies the necessary viable cells, protein signaling, and extracellular matrix (ECM) scaffold found in fresh cartilage in order to facilitate a positive clinical outcome for cartilage defect replacement and repair. Methods: Viability testing was performed by digestion of the graft, cells were counted using a trypan blue assay. Growth factor and ECM protein content was quantified using biochemical assays. A fixation model was introduced to assess tissue outgrowth capability and cellular metabolic activity in vitro . Histological and immunofluorescence staining were employed to confirm tissue architecture, cellular outgrowth, and presence of ECM. The effects of the T-LE Allograft to signal bone marrow-derived mesenchymal stem cell (BM-MSC) migration and chondrogenic differentiation were evaluated using in vitro co-culture assays. Immunogenicity testing was completed using flow cytometry analysis of cells obtained from digested T-LE Allografts and fresh articular cartilage. Results: Average viability of the T-LE Allograft post-thaw was found to be 94.97 ±3.38%, compared to 98.83 ±0.43% for fresh articular cartilage. Explant studies from the in vitro fixation model confirmed the long-term viability and proliferative capacity of these chondrocytes. Growth factor and ECM proteins were quantified for the T-LE Allograft revealing similar profiles to fresh articular cartilage. Cellular signaling of the T-LE Allograft and fresh articular cartilage both exhibited similar outcomes in co-culture for migration and differentiation of BM-MSCs. Flow cytometry testing confirmed the T-LE Allograft is immune-privileged as it is negative for immunogenic markers and positive for chondrogenic markers. Conclusions: Using our novel, proprietary cryopreservation method, the T-LE Allograft retains excellent cellular viability, with native-like growth factor and ECM composition of healthy cartilage after two years of storage at -80 o C. The successful cryopreservation of the T-LE Allograft alleviates the limited availably of conventionally used fresh osteochondral allograft (OCA), by providing a readily available and simple to use allograft solution. The results presented in this paper supports clinical data that the T-LE Allograft can be a successful option for repairing chondral defects.

scholarly journals AFM-Based Method for Measurement of Normal and Osteoarthritic Human Articular Cartilage Surface Roughness

Materials ◽  
2020 ◽  
Vol 13 (10) ◽  
pp. 2302 ◽  
Author(s):  
Mikhail Ihnatouski ◽  
Jolanta Pauk ◽  
Dmitrij Karev ◽  
Boris Karev
Keyword(s):  
Atomic Force Microscopy ◽  
Articular Cartilage ◽  
Young’S Modulus ◽  
Young's Modulus ◽  
Human Articular Cartilage ◽  
Roughness Parameters ◽  
Arithmetic Average ◽  
Force Microscopy ◽  
Atomic Force ◽  
Healthy Cartilage

In osteoarthrosis, pathological features of articular cartilage are associated with degeneration and nanomechanical changes. The aim of this paper is to show that indentation-atomic force microscopy can monitor wear-related biomechanical changes in the hip joint of patients with osteoarthritis. Fifty patients (N = 50), aged 40 to 65, were included in the study. The mechanical properties and the submicron surface morphology of hyaline cartilage were investigated using atomic force microscopy. Measurements of the roughness parameters of cartilage surfaces were performed, including the arithmetic average of absolute values (Ra), the maximum peak height (Rp), and the mean spacing between local peaks (S). The arithmetic mean of the absolute values of the height of healthy cartilage was 86 nm, while wear began at Ra = 73 nm. The maximum changes of values of the roughness parameters differed from the healthy ones by 71%, 80%, and 51% for Ra, Rp, and S, respectively. Young’s modulus for healthy cartilage surfaces ranged from 1.7 to 0.5 MPa. For the three stages of cartilage wear, Young’s modulus increased, and then it approached the maximum value and decreased. AFM seems to be a powerful tool for surface analysis of biological samples as it enables indentation measurements in addition to imaging.

scholarly journals The Relationship Between Proteoglycan Loss, Overloading-Induced Collagen Damage, and Cyclic Loading in Articular Cartilage

Cartilage ◽  
2019 ◽  
pp. 194760351988500
Author(s):  
Lorenza Henao-Murillo ◽  
Maria-Ioana Pastrama ◽  
Keita Ito ◽  
Corrinus C. van Donkelaar
Keyword(s):  
Articular Cartilage ◽  
Cyclic Loading ◽  
Mechanical Loading ◽  
Mechanical Tests ◽  
Repeated Loading ◽  
Healthy Cartilage ◽  
Before And After ◽  
Damage Grades ◽  
The Relationship ◽  
Phosphate Buffered Saline

Objective The interaction between proteoglycan loss and collagen damage in articular cartilage and the effect of mechanical loading on this interaction remain unknown. The aim of this study was to answer the following questions: (1) Is proteoglycan loss dependent on the amount of collagen damage and does it depend on whether this collagen damage is superficial or internal? (2) Does repeated loading further increase the already enhanced proteoglycan loss in cartilage with collagen damage? Design Fifty-six bovine osteochondral plugs were equilibrated in phosphate-buffered saline for 24 hours, mechanically tested in compression for 8 hours, and kept in phosphate-buffered saline for another 48 hours. The mechanical tests included an overloading step to induce collagen damage, creep steps to determine tissue stiffness, and cyclic loading to induce convection. Proteoglycan release was measured before and after mechanical loading, as well as 48 hours post-loading. Collagen damage was scored histologically. Results Histology revealed different collagen damage grades after the application of mechanical overloading. After 48 hours in phosphate-buffered saline postloading, proteoglycan loss increased linearly with the amount of total collagen damage and was dependent on the presence but not the amount of internal collagen damage. In samples without collagen damage, repeated loading also resulted in increased proteoglycan loss. However, repeated loading did not further enhance the proteoglycan loss induced by damaged collagen. Conclusion Proteoglycan loss is enhanced by collagen damage and it depends on the presence of internal collagen damage. Cyclic loading stimulates proteoglycan loss in healthy cartilage but does not lead to additional loss in cartilage with damaged collagen.

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