scholarly journals Establishment of an Ex Vivo Inflammatory Osteoarthritis Model With Human Osteochondral Explants

2021 ◽  
Vol 9 ◽  
Author(s):  
Kaihu Li ◽  
Penghui Zhang ◽  
Yong Zhu ◽  
Mauro Alini ◽  
Sibylle Grad ◽  
...  
Keyword(s):  
Femoral Head ◽  
Matrix Metalloproteinase ◽  
Ex Vivo ◽  
Degenerative Joint Disease ◽  
New Drugs ◽  
Joint Disease ◽  
Control Group ◽  
Pathophysiological Mechanism ◽  
Superficial Zone ◽  
Matrix Metalloproteinase 1

Osteoarthritis (OA) is the most common degenerative joint disease without clear pathophysiological mechanism and effective drugs for treatment. Although various animal models exist, the translation of the outcome into clinics remains difficult due to species differences. In this study, an ex vivo inflammatory OA model was induced using different concentrations of interleukin one beta (IL-1β) and tumor necrosis factor α (TNF-α) on explants from the human femoral head. In the inflammatory OA groups, the gene expression levels of cartilage catabolism (matrix metalloproteinase 1 (MMP1), matrix metalloproteinase 3 (MMP3)), and inflammation (interleukin 6 (IL-6), interleukin 8 (IL-8)) markers were significantly upregulated, while the anabolic genes (collagen 2 (COL2), aggrecan (ACAN), and proteoglycan 4 (PRG4)) were downregulated compared to the control group. The release of cytokines (IL-6, IL-8) and nitric oxide (NO) in the conditioned medium was also upregulated in inflammatory OA groups. The Safranin O/Fast Green staining showed loss of proteoglycan in the superficial zone cartilage after cytokine treatment. The results indicated that an ex vivo inflammation and degeneration model was successfully established using osteochondral explants from the human femoral head. This model can be used to elucidate the in-depth mechanism of inflammatory OA and to screen new drugs for OA treatment.

scholarly journals Disease-Modifying Potential of Metformin and Alendronate in an Experimental Mouse Model of Osteoarthritis

Biomedicines ◽  
2021 ◽  
Vol 9 (8) ◽  
pp. 1017
Author(s):  
Lyudmila Belenska-Todorova ◽  
Sevdalina Nikolova Lambova ◽  
Stela Stoyanova ◽  
Elenka Georgieva ◽  
Tsvetelina Batsalova ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Cells ◽  
Ex Vivo ◽  
Histopathological Examination ◽  
Marrow Cell ◽  
Chronic Phase ◽  
Serum Levels ◽  
Degenerative Joint Disease ◽  
Joint Disease ◽  
Control Group

Osteoarthritis (OA) is the most common degenerative joint disease causing progressive damages of the cartilage and subchondral bone, synovial inflammation, and severe pain. Despite the complex pathomorphological changes that occur in OA, the approach to different forms of OA is standardized. The global results from pharmacological treatment are not satisfactory. Hence, this study aimed to explore the effects of metformin, alendronate, and their combination on OA development and progression in mice with collagenase-induced osteoarthritis (CIOA). Female ICR (CD-2) mice were randomized to five groups: control group, CIOA untreated, CIOA + metformin, CIOA + alendronate, and CIOA + metformin + alendronate. OA was induced by the intra-articular (i.a.) injection of collagenase. OA phenotype was analyzed by flow cytometry (bone marrow cell differentiation), ELISA (serum levels of the adipokines leptin and resistin), and histology (pathological changes of the knee joint). Treatment with metformin, alendronate, or their combination inhibited the expression of RANK and RANKL on osteoblasts and osteoclasts obtained by ex vivo cultivation of bone marrow cells in mineralization or osteoclastogenic media. In addition, metformin treatment was effective for the attenuation of fibroblast differentiation, but not of mesenchymal stem cells (MSCs), while alendronate had an opposite effect. The combination of metformin and alendronate had a suppressive effect on both MSCs and fibroblasts differentiation. Treatment with metformin, alendronate, and their combination decreased serum concentrations of leptin and resistin in the chronic phase of arthritis. The histopathological examination showed that compared with the untreated CIOA group (OA score 9), the groups treated with metformin (OA score 4) or alendronate (OA score 6) had lower scores for cartilage changes. Metformin combined with alendronate significantly decreased the degree of cartilage degeneration (OA score 2), suggesting that this combination might be a useful approach for the treatment of OA patients.

scholarly journals The Effect of Mesenchymal Stem Cell Wharton's Jelly on Matrix Metalloproteinase-1 and Interleukin-4 Levels in Osteoarthritis Rat Model

2019 ◽  
Vol 7 (4) ◽  
pp. 529-535 ◽  
Author(s):  
Endrinaldi Endrinaldi ◽  
Eryati Darwin ◽  
Nasrul Zubir ◽  
Gusti Revilla
Keyword(s):  
Stem Cell ◽  
Mesenchymal Stem Cell ◽  
Matrix Metalloproteinase ◽  
Joint Disease ◽  
Interleukin 4 ◽  
Target Component ◽  
Control Group ◽  
Control Group Design ◽  
Matrix Metalloproteinase 1

BACKGROUND: Osteoarthritis (OA) is generally considered a degenerative joint disease caused by biomechanical changes and the ageing process. In OA pathogenesis, the development of OA is thought to be regulated largely by excess matrix metalloproteinase (MMP), which contributes to the degradation of extracellular matrices such as MMP-1 and Interleukin-4. AIM: This study aims to prove the influence of Mesenchymal Stem Cell Wharton Jelly on decreasing MMP-1 levels and increasing IL-4 which is a specific target as a target component in cases of osteoarthritis in vivo. MATERIAL AND METHODS: This research is an experimental study with the design of Post-Test-Only Control Group Design. The sample consisted of 16 OA rats as a control group and 16 OA rats treated with MSC-WJ as a treatment group. OA induction is done by injection of monosodium iodoacetate (MIA) into the intra-articular right knee. Giving MSC-WJ is done in the third week after MIA induction. The serum MMP-1 and IL-4 levels were measured after 3 weeks treated with MSC-WJ using the ELISA method. The statistical test used is an independent t-test. The value of p < 0.05 was said to be statistically significant. RESULTS: The result showed that serum MMP-1 levels were higher in the group treated with MSC-WJ than in the control group (p < 0.05). Serum IL-4 levels were higher in the group treated with MSC-WJ than in the control group (p < 0.05). CONCLUSION: This study concluded that MSC-WJ increased MMP-1 levels and IL-4 levels in serum OA rats. MSC-WJ showed a negative effect on MMP-1 in the serum of OA rats.

A method for visualizing the dorsal acetabular rim and the coverage of the femoral head

2001 ◽  
Vol 14 (03) ◽  
pp. 151-155 ◽  
Author(s):  
J. Hoskinson ◽  
W. C. Renberg
Keyword(s):  
Femoral Head ◽  
Hip Joint ◽  
Prognostic Value ◽  
Degenerative Change ◽  
Femoral Shaft ◽  
Normal Activity ◽  
Degenerative Joint Disease ◽  
Joint Disease ◽  
Anatomical Landmarks ◽  
Acetabular Rim

SummaryThe authors describe a new technique to visualize the dorsal acetabular rim and the coverage of the femoral head in the nonsedated dog. The technique involves using an overhead beam, directed at an angle tangential to the dorsal rim of the acetabulum, with a film positioned caudal to the standing dog. Anatomical landmarks that can routinely be identified include: the ilial crest, ilial shaft, ischial tuberosity, acetabulum, acetabular rim (particularly the dorsocaudal component), femoral head, greater trochanter, femoral neck, femoral shaft, rectum and the tail. Because the animal is standing and is not sedated, the technique may have additional value as a means of evaluating subluxation of the hip joint. It maintains a posture as close as possible to that experienced by the animal in normal activity. If the technique has prognostic value in that regard, more investigation is needed, but it is useful in itself as a technique to visualize the area of the acetabulum.A new radiographic technique to evaluate the canine hip joint is described. The view involves tangential projection of the acetabulum in the standing, awake dog. Nineteen dogs have been radiographed to develop the technique and the method has been found to be technically simple and consistent. It allows examination of the dorsal acetabular rim and may help examine the amount of subluxation of the hip as well as the presence of any degenerative joint disease. The authors advocate additional study to determine the technique’s prognostic value in predicting degenerative change associated with hip dysplasia.

scholarly journals Outcome of tantalum rod insertion in the treatment of osteonecrosis of the femoral head with minimum follow-up of 1 year: a meta-analysis and systematic review

2020 ◽  
Vol 7 (2) ◽  
pp. 329-339
Author(s):  
James Randolph Onggo ◽  
Mithun Nambiar ◽  
Jason Derry Onggo ◽  
Guan Tay ◽  
Parminder J Singh ◽  
...  
Keyword(s):  
Femoral Head ◽  
Subgroup Analysis ◽  
Bone Grafting ◽  
Meta Analysis ◽  
Degenerative Joint Disease ◽  
Joint Disease ◽  
Safe Alternative ◽  
Meta Analyses ◽  
Marginal Risk

Abstract Osteonecrosis of the femoral head (ONFH) is a debilitating disease that can cause deformity and collapse of the femoral head, thus leading to the development of degenerative joint disease that can incapacitate the patient with pain and reduction in hip mobility. This study aims to determine the safety and efficacy of tantalum rod insertion in the treatment of ONFH with a minimum follow-up period of 1 year. A multi-database search was performed according to Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines. Data from studies assessing the clinical and radiological outcomes as well as complications of tantalum rod insertion in the treatment of ONFH with a minimum follow-up period of 1 year were extracted and analyzed. Ten studies were included in this meta-analysis, consisting of 550 hips. There was a statistically significant increase in HHS (MD = 30.35, 95% CI: 20.60–40.10, P &lt; 0.001) at final follow-up versus pre-operative scores. The weighted pooled proportion (PP) of radiographic progression of ONFH was 0.221 (95% CI: 0.148–0.316), while that of progression into femoral head collapse was 0.102 (95% CI: 0.062–0.162). Conversion to total hip arthroplasty (THA) had a PP of 0.158 (95% CI: 0.107–0.227) with a mean weighted period of 32.4 months (95% CI: 24.9–39.9 months). Subgroup analysis of conversion to THA when tantalum rods were used in conjunction with bone grafting (PP = 0.150, 95% CI: 0.092–0.235) showed a marginal risk reduction than when compared with subgroup analysis of tantalum rods being used alone (PP = 0.154, 95% CI: 0.078–0.282). Tantalum rod is a safe alternative option to the current joint-preserving procedures available in the treatment of ONFH. However, more studies are needed to investigate and identify the most appropriate patients who would benefit most and the synergistic effect brought on by the use of complementary biological augmentation of bone grafting or stem cells with tantalum rods.

scholarly journals Effects of chondroitin sulfate and sodium hyaluronate on chondrocytes and extracellular matrix of articular cartilage in dogs with degenerative joint disease

2008 ◽  
Vol 60 (1) ◽  
pp. 93-102 ◽  
Author(s):  
G. Gonçalves ◽  
E.G. Melo ◽  
M.G. Gomes ◽  
V.A. Nunes ◽  
C.M.F. Rezende
Keyword(s):  
Articular Cartilage ◽  
Chondroitin Sulfate ◽  
Sodium Hyaluronate ◽  
Nucleolar Organizer ◽  
Degenerative Joint Disease ◽  
Joint Disease ◽  
Control Group ◽  
Nucleolar Organizer Regions ◽  
Morphological Evaluation ◽  
Cell Counts

Samples of articular cartilage of femur, tibia and patella of 15 dogs with experimentally induced degenerative joint disease (DJD) were microscopically analyzed. Animals were distributed into three groups (n=5): the control group received no medication; the second group was treated with chondroitin sulfate and the third received sodium hyaluronate. Samples were processed and stained with HE and toluidine blue for morphological evaluation. The metabolic and proliferative activity of the chondrocytes was evaluated by the measurement of nucleolar organizer regions (NORs) after impregnation by silver nitrate. Significant differences were not observed (P>0.05) in the morphology among the groups, however, the group treated with sodium hyaluronate had a higher score suggesting a trend to a greater severity of the lesions. Significant differences were not observed (P>0.05) in the measurement of NORs, cells and NORs/cells among the groups. Although differences were not significant, sodium hyaluronate group showed higher NOR and cell counts which suggested an increase of the proliferation rate of chondrocytes. In addition, a higher NOR/cell ratio in the group treated with chondroitin sulfate suggested that this drug may have stimulated the metabolic activity of the chondrocytes, minimizing the lesions resulting from DJD.

scholarly journals New Therapeutic Strategies for Osteoarthritis by Targeting Sialic Acid Receptors

Biomolecules ◽  
2020 ◽  
Vol 10 (4) ◽  
pp. 637 ◽  
Author(s):  
Paula Carpintero-Fernandez ◽  
Marta Varela-Eirin ◽  
Alessandra Lacetera ◽  
Raquel Gago-Fuentes ◽  
Eduardo Fonseca ◽  
...  
Keyword(s):  
Articular Cartilage ◽  
Ex Vivo ◽  
Molecular Model ◽  
Cartilage Degradation ◽  
Degenerative Joint Disease ◽  
Joint Disease ◽  
Novel Therapy ◽  
Human Cartilage ◽  
Sialic Acid Receptors ◽  
Cartilage Breakdown

Osteoarthritis (OA) is the most common degenerative joint disease characterized by articular cartilage degradation and joint degeneration. The articular cartilage is mainly formed by chondrocytes and a collagen-proteoglycan extracellular matrix that contains high levels of glycosylated proteins. It was reported that the shift from glycoproteins containing α-2,6-linked sialic acids to those that contain α-2,3 was associated with the onset of common types of arthritis. However, the pathophysiology of α-2,3-sialylation in cartilage has not been yet elucidated. We show that cartilage from osteoarthritic patients expresses high levels of the α-2,3-sialylated transmembrane mucin receptor, known as podoplanin (PDPN). Additionally, the Maackia amurensis seed lectin (MASL), that can be utilized to target PDPN, attenuates the inflammatory response mediated by NF-kB activation in primary chondrocytes and protects human cartilage breakdown ex vivo and in an animal model of arthritis. These findings reveal that specific lectins targeting α-2,3-sialylated receptors on chondrocytes might effectively inhibit cartilage breakdown. We also present a computational 3D molecular model for this interaction. These findings provide mechanistic information on how a specific lectin could be used as a novel therapy to treat degenerative joint diseases such as osteoarthritis.

Traumatic Coxofemoral Luxation in Dysplastic Dogs Managed with a Triple Pelvic Osteotomy: Results in four Dogs

1997 ◽  
Vol 10 (03) ◽  
pp. 136-140 ◽  
Author(s):  
D. D. Lewis ◽  
S. C. Kerwin ◽  
S. T. Murphy
Keyword(s):  
Femoral Head ◽  
Hip Dysplasia ◽  
External Rotation ◽  
Pelvic Osteotomy ◽  
Degenerative Joint Disease ◽  
Joint Disease ◽  
Contralateral Limb ◽  
Norberg Angle

SummaryTriple pelvic osteotomy (TPO) was used in the treatment for traumatic coxofemoral luxations in four adult, large breed dogs with hip dysplasia. Initial closed reductions failed in three and one dog had an initial closed reduction and subsequent open reduction of the coxofemoral luxation that failed. Hip dysplasia was thought to be a prominent factor contributing to the reluxation. TPO successfully maintained reduction of the coxofemoral luxation in all of the dogs. An increase in dorsal acetabular coverage of the femoral head following TPO was demonstrated by an increased Norberg angle. The improved congruency was thought to maintain reduction of the femoral head in the acetabulum and decrease stresses on the joint capsule, allowing healing to occur. Long-term (median: 343, mean ± SD: 406 ± 226 days follow-up) function of the affected limb was comparable to the contralateral limb. Three of the four dogs did not have radiographic progression of coxofemoral degenerative joint disease of the affected joint and differences in the progression of degenerative joint disease were not evident between the affected and the contralateral coxofemoral joint. A decrease in abduction and external rotation and an increase in internal rotation following TPO was noted in the affected coxofemoral joint. Our results establish the utility of this procedure in dysplastic dogs with traumatic coxofemoral luxations.Triple pelvic osteotomy used in the treatment for traumatic coxofemoral luxation in four adult, large breed dogs with hip dysplasia successfully maintained reduction and resulted in satisfactory limb function in all patients.

Avulsion Fractures of the Femoral Head: Internal Fixation Using a Ventral Approach to the Hip Joint

1997 ◽  
Vol 10 (01) ◽  
pp. 23-26 ◽  
Author(s):  
P. M. Montavon ◽  
H. F. L’Eplattenier
Keyword(s):  
Femoral Head ◽  
Surgical Technique ◽  
Hip Joint ◽  
Cartilage Damage ◽  
Kirschner Wire ◽  
Degenerative Joint Disease ◽  
Joint Disease ◽  
Joint Surface ◽  
Avulsion Fractures ◽  
Lag Screw

SummaryAvulsion fractures of the femoral head are encountered in conjunction with craniodorsal luxations of the hip joint and cannot be treated conservatively without risking either reluxation of the joint or considerable cartilage damage resulting in degenerative joint disease. Fixation of the fragment is possible by inserting a Kirschner wire and a lag screw from the articular surface, making sure the implants are well countersunk. A ventromedial approach to the hip joint allows good visibility of the joint surface and easy reduction of the fracture without severing the round ligament. The surgical technique described was used on three cases and combines a ventromedial approach to the hip joint with fixation of the fracture with a Kirschner wire and a lag screw inserted from the joint surface, and has the advantages of enabling good reconstruction of the joint surface as well as maintaining postoperative joint stability. Both these factors considerably reduce the development of degenerative joint disease and improve the prognosis for recovery of full limb function.A surgical technique for treatment of avulsion fractures of the femoral head is described. It combines a ventromedial approach to the hip joint with fixation of the fracture with a Kirschner wire and a lag screw inserted from the joint surface.

Condylar changes in patients with idiopathic condylar resorption: retrospective 2-year follow-up CBCT-based case–control study

2020 ◽  
Vol 42 (6) ◽  
pp. 619-625
Author(s):  
Cristina R Exposto ◽  
Peter Stoustrup ◽  
Kasper D Kristensen ◽  
Michel Dalstra ◽  
Thomas K Pedersen
Keyword(s):  
Case Control Study ◽  
Qualitative Evaluation ◽  
Vertical Displacement ◽  
Case Control ◽  
Degenerative Joint Disease ◽  
Joint Disease ◽  
Control Group ◽  
Radiological Appearance ◽  
Control Study

Summary Objectives To compare condylar development and changes in condylar radiological appearance in patients with idiopathic condylar resorption (ICR) to a healthy, age- and gender matched, control group. Materials and methods This case-control study included 16 ICR patients [mean age: 15years, 9 months; standard deviation (SD): 4 years) and 16 controls (mean age: 16 years, 8 months; SD: 4 years, 7 months), with diagnostic (T0) and 2-year follow-up (T1) CBCT examinations. Condylar changes were evaluated through changes in condylar neck angle (CNA), and the transversal, vertical and anteroposterior displacement of five condylar points between T0 and T1. The magnitude and direction of condylar changes were evaluated using vector analyses. A qualitative radiological evaluation of the TMJ was performed based on healthy, erosive and repaired morphological appearance. Linear and angular measurements were assessed using ANOVA and a Tukey post-hoc test, and vectors were tested using an independent-sample 2-tailed t-test. Fisher’s exact test was used for the qualitative evaluation. Results At T0, ICR patients exhibited decreased condylar height, smaller condylar width and posteriorly inclined CNA compared with the control group (P &lt; 0.05). During observation, condylar vertical growth was smaller in the ICR group than in the control group (P &lt; 0.05). Vector analysis showed an upward direction of vertical displacement for all condylar points in the control group; the ICR group showed a downward direction (P &lt; 0.003). The radiological appearance of 75% of the ICR condyles and 94% of the control condyles did not change during the 2-year follow-up period. Conclusions ICR condyles displayed reduced vertical development compared with control condyles. The radiological appearance remained unchanged for most joints. Observed changes in radiological appearance did not always follow a progressive model of degenerative joint disease.

ETA-receptor blockade prevents matrix metalloproteinase activation late postmyocardial infarction in the rat

2001 ◽  
Vol 280 (3) ◽  
pp. H984-H991 ◽  
Author(s):  
Bruno K. Podesser ◽  
Deborah A. Siwik ◽  
Franz R. Eberli ◽  
Flora Sam ◽  
Soeun Ngoy ◽  
...  
Keyword(s):  
Matrix Metalloproteinases ◽  
Matrix Metalloproteinase ◽  
Ex Vivo ◽  
Systolic Pressure ◽  
Left Ventricular ◽  
Control Group ◽  
Receptor Blockade ◽  
Postmyocardial Infarction ◽  
Eta Receptor ◽  
Stimulation Of

Endothelin (ET) A (ETA) receptors activate matrix metalloproteinases (MMP). Since endothelin-1 (ET) is increased in myocardium late postmyocardial infarction (MI), we hypothesized that stimulation of ETA receptors contributes to activation of myocardial MMPs late post-MI. Three days post-MI, rats were randomized to treatment with the ETA-selective receptor antagonist sitaxsentan ( n = 12) or a control group ( n = 12). Six weeks later, there were rightward shifts of the left ventricular (LV) end-diastolic and end-systolic pressure-volume relationships, as measured ex vivo by the isovolumic Langendorff technique. Both shifts were markedly attenuated by sitaxsentan. In LV myocardium remote from the infarct, the activities of MMP-1, MMP-2, and MMP-9 were increased in the post-MI group, and the increases were prevented by sitaxsentan treatment. Expression of tissue inhibitor of MMP-1 was decreased post-MI, and the decrease was prevented by sitaxsentan treatment. Chronic post-MI remodeling is associated with activation of MMPs in myocardium remote from the infarct. Inhibition of ETAreceptors prevents MMP activation and LV dilation, suggesting that ET, acting via the ETA receptor, contributes to chronic post-MI remodeling by its effects on MMP activity.

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