scholarly journals A New Method to Develop the Primate Model of Knee Osteoarthritis With Focal Cartilage Defect

Author(s):  
Xin Bi ◽  
Tao Li ◽  
Min Li ◽  
Shutian Xiang ◽  
Junhong Li ◽  
...  

Objective: Osteoarthritis (OA) is a common degenerative joint disease, and animal models have proven pivotal in investigating this disease. This study aimed to develop a primate model of OA that may be more relevant to research studies on OA in humans.Method: Twelve female rhesus macaques were randomly divided into three groups. Four animals were untreated (Control group); four were subjected to the modified Hulth method, involving cutting of the anterior and posterior cruciate ligaments, and transecting the meniscus (Hulth group); and four were subjected to the modified Hulth method combined with cartilage defect (MHCD group). Each primate was subjected to motor ability tests, and underwent arthroscopic, radiographic, morphological, and pathological observation of the knee joints at various times for up to 180 days.Results: Motor ability on Day 180 was significantly lower in the MHCD group than in the Control (p<0.01) and Hulth (p<0.05) groups. Radiographic and morphological examination showed that the severity of knee joint deformity and articular cartilage injury were greater in the MHCD group than in the other groups. Pathological examination showed that cartilage thickness was significantly lower in the MHCD group than in the other groups at the same time points. The Mankin score on Day 180 was markedly higher in the MHCD group than in the Hulth (p<0.05) and Control (p<0.001) groups.Conclusion: The MHCD model of OA closely resembles the pathophysiological processes of spontaneous knee OA in humans. The time required to develop knee OA is shorter using the MHCD model than using the Hulth method.

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Ashwani Kesarwani ◽  
Parul Sahu ◽  
Kshama Jain ◽  
Prakriti Sinha ◽  
K. Varsha Mohan ◽  
...  

AbstractDue to the limited utility of Bacillus Calmette–Guérin (BCG), the only approved vaccine available for tuberculosis, there is a need to develop a more effective and safe vaccine. We evaluated the safety and efficacy of a dry powder aerosol (DPA) formulation of BCG encapsulated alginate particle (BEAP) and the conventional intradermal BCG immunization in infant rhesus macaques (Macaca mulatta). The infant macaques were immunized intratracheally with DPA of BEAP into the lungs. Animals were monitored for their growth, behaviour, any adverse and allergic response. The protective efficacy of BEAP was estimated by the ex-vivo H37Rv infection method. Post-immunization with BEAP, granulocytes count, weight gain, chest radiography, levels of liver secreted enzymes, cytokines associated with inflammation like TNF and IL-6 established that BEAP is non-toxic and it does not elicit an allergic response. The T cells isolated from BEAP immunized animals’ blood, upon stimulation with M.tb antigen, secreted high levels of IFN-γ, TNF, IL-6 and IL-2. The activated T cells from BEAP group, when co-cultured with M.tb infected macrophages, eliminated largest number of infected macrophages compared to the BCG and control group. This study suggests the safety and efficacy of BEAP in Non-human primate model.


2020 ◽  
Author(s):  
Huanhuan JIA ◽  
Meili CHEN ◽  
Xiaoling LUO ◽  
Gang HOU ◽  
Ting LUO ◽  
...  

Abstract Background Ankylosing spondylitis (AS) is a progressive, disabling joint disease that affects millions worldwide. There is a lack of useful disease model to conduct comprehensive mechanistic studies. Non-human primate model is a potential spontaneous model for ankylosing spondylitis (AS). Methods A group of cynomolgus monkeys with abnormal joints and abnormal movements were screened out from about 20,000 cynomolgus monkeys primarily. A 2-years follow-up study of this group of cynomolgus monkeys having joint lesions reported of spinal stiffness was performed by conducting hematological testing, radiographic examination, family aggregation analysis, pathological analysis and genetic testing. Results These diseased animals suffered from spontaneous AS with clinical features recapitulating human AS disease progression. The spontaneous incidence rate and the onset age of AS in monkeys similar to epidemiological features of AS patients. The disease progression in disease monkeys have shown bone erosion, osteophyte formation and “Bamboo-like” change. ESR, CRP IL-17, TNF-α and VEGF levels significantly increase in AS monkeys comparing with normal monkeys. Several features similar to AS patients, including cartilage destruction, cartilage ossification, chondroid metaplasia and bone formation were shown in AS monkeys pathological examination results. Both the serum bone resorption and bone formation biomarkers of AS monkeys were significantly reduce. In our current SNP sequencing results, loci that similar to AS-relative SNPs in human genome have not yet been found. Conclusions The study offers a promising non-human primate model for spontaneous ankylosing spondylitis which may serve as an excellent substitute for its pre-clinical research.


2021 ◽  
Vol 61 (1) ◽  
Author(s):  
Patricia Gabrielli Vassão ◽  
Ana Carolina Flygare de Souza ◽  
Raquel Munhoz da Silveira Campos ◽  
Livia Assis Garcia ◽  
Helga Tatiana Tucci ◽  
...  

Abstract Background The knee osteoarthritis (OA) is a joint disease characterized by degradation of articular cartilage that leads to chronic inflammation. Exercise programs and photobiomodulation (PBM) are capable of modulating the inflammatory process of minimizing functional disability related to knee OA. However, their association on the concentration of biomarkers related to OA development has not been studied yet. The aim of the present study is to investigate the effects of PBM (via cluster) with a physical exercise program in functional capacity, serum inflammatory and cartilage degradation biomarkers in patients with knee OA. Methods Forty-two patients were randomly allocated in 3 groups: ESP: exercise + sham PBM; EAP: exercise + PBM and CG: control group. Six patients were excluded before finished the experimental period. The analyzed outcomes in baseline and 8-week were: the Western Ontario and McMaster Universities Osteoarthritis (WOMAC) and the evaluation of serum biomarkers concentration (IL-1β, IL-6, IL-8, IL-10 e TNF-α, and CTX-II). Results An increase in the functional capacity was observed in the WOMAC total score for both treated groups (p < 0.001) and ESP presents a lower value compared to CG (p < 0.05) the 8-week post-treatment. In addition, there was a significant increase in IL-10 concentration of EAP (p < 0.05) and higher value compared to CG (p < 0.001) the 8-week post-treatment. Moreover, an increase in IL-1β concentration was observed for CG (p < 0.05). No other difference was observed comparing the other groups. Conclusion Our data suggest that the physical exercise therapy could be a strategy for increasing functional capacity and in association with PBM for increasing IL-10 levels in OA knee individuals. Trial registration: ReBEC (RBR-7t6nzr).


2021 ◽  
Vol 17 ◽  
Author(s):  
Muhammad Tariq Rafiq ◽  
Mohamad Shariff A Hamid ◽  
Eliza Hafiz ◽  
Farid Ahmad Chaudhary ◽  
Muhammad Irfan Khan

Introduction: Knee osteoarthritis (OA) is a weight-bearing joint disease and more common in the overweight and obese persons. The objective of the study was to assess the feasibility and acceptability of instructions of daily care (IDC) on pain, mobility and body mass index (BMI) among knee OA participants who are overweight or obese. Material and Method: The study was an open-label randomized controlled trial of six-weeks. Forty overweight and obese participants with knee OA were randomly divided into two groups by a computer-generated number. The participants in the Instruction Group (IG) were provided with leaflets explaining IDC for the duration of six-weeks. Both groups were instructed to take low doses of the non-steroid anti-inflammatory drug (NSAIDs) on alternate days. The outcome measures were pain, mobility and BMI. The feasibility and acceptability of knee pain and mobility were assessed using a questionnaire designed by experts in rehabilitation. Results: Participants in the IG reported more statistically significant pain relief as assessed by the Western Ontario and McMaster Universities Osteoarthritis Index score (p=0.001) and improvement in mobility (p=0.000) assessed by the Timed Up and Go test score after six weeks compared to the Control Group (CG). Both groups did not demonstrate any significant change in BMI (p-value > 0.05), The results of descriptive statistics showed a significantly higher satisfaction score to participants who received a combination of IDC and NSAIDs, indicating an acceptable intervention. Conclusion: The IDC are effective and acceptable in terms of improving pain and mobility and should be recommended as the usual care of treatment.


2020 ◽  
Author(s):  
Genevieve Housman ◽  
Ellen E. Quillen ◽  
Anne C. Stone

AbstractObjectiveEpigenetic factors, such as DNA methylation, play an influential role in the development of the degenerative joint disease osteoarthritis (OA). These molecular mechanisms have been heavily studied in humans, and although OA affects several other animals in addition to humans, few efforts have taken an evolutionary perspective. This study explores the evolution of OA epigenetics by assessing the relationship between DNA methylation variation and knee OA development in baboons (Papio spp.) and by comparing these findings to human OA epigenetic associations.MethodsGenome-wide DNA methylation patterns were identified in bone and cartilage of the right distal femora from 56 pedigreed, adult baboons (28 with and 28 without knee OA) using the Illumina Infinium MethylationEPIC BeadChip.ResultsSeveral significantly differentially methylated positions (DMPs) and regions (DMRs) were found between tissue types. Substantial OA-related differential methylation was also identified in cartilage, but not in bone, suggesting that cartilage epigenetics may be more influential in OA than bone epigenetics. Additionally, some genes containing OA-related DMPs overlap with and display methylation patterns similar to those previously identified in human OA, revealing a mixture of evolutionarily conserved and divergent OA-related methylation patterns in primates.ConclusionsOverall, these findings reinforce current etiological perspectives of OA and enhance our evolutionary understanding of epigenetic mechanisms associated with OA. This work further establishes baboons as a valuable nonhuman primate model of OA, and continued investigations in baboons will help to disentangle the molecular mechanisms contributing to OA and their evolutionary histories.


2020 ◽  
Vol 10 (03) ◽  
pp. 448-453
Author(s):  
Zindan Y. Ameen ◽  
Najlaa K. Issa

The major famous degenerative joint disease is osteoarthritis (OA), which leads to disability, reduced motion, pain, swelling, and crepitus. Thus, this research aimed to determine the statuses of oxidative stress (OS) and antioxidants in blood patients with primary OA and to compare serum levels of some inflammatory markers between control and knee OA patients groups. In this case-control study, 126 knee OA patients and 49 control individuals were taken, who visited the Center of Rheumatoid in Duhok city, Kurdistan region of Iraq. For the participant’s information, a study questionnaire was employed. Serum total bilirubin (TBIL), uric acid (UA), catalase, peroxynitrite (PN), malondialdehyde (MDA), and ceruloplasmin (CP) were evaluated. Some inflammatory markers were measured, including erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP). Also, body mass index (BMI) was measured. In the present study, the % of the control group was 28% and patients groups were 29.71, 28, and 14.29% for mild, moderate, and severe cases, respectively. The mean values of MDA and CP showed significant differences between knee OA and control groups. On the other hand, the mean values of catalase, PN, UA, and TBIL showed no significant differences among control and knee OA groups. A significant difference was found among control and knee OA groups for ESR, but CRP was non-significant. In the current study, elevated levels of lipid-peroxidation and CP in patients with knee OA were observed. OS may be involved in OA.


2020 ◽  
Vol 8 (B) ◽  
pp. 350-357
Author(s):  
Vivi Sofia ◽  
Moch Saiful Bachri ◽  
Endrinaldi Endrinaldi

BACKGROUND: Osteoarthritis (OA) is a degenerative joint disease in one or more joints characterized by changes in pathological structures such as cartilage, hypertrophy, and remodeling of the subchondral bone and secondary inflammation of the synovium membrane, causing changes in joint components such as cells, matrices, and molecular production. At the molecular level, an imbalance between catabolic and anabolic activities in joint cartilage results in OA. Nuclear factor kappa beta (NFκβ) is a cytokine that plays an important role in the signaling pathway of the pathogenesis of OA in causing an inflammatory reaction, whereas interleukin (IL)-10 is an anti-inflammatory cytokine that is involved in the pathogenesis of OA. AIM: This study aims to prove the influence before and after administration mesenchymal stem cells from Wharton’s jelly on the serum NFκβ and IL-10 levels in OA rat models. MATERIALS 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 3rd week after MIA induction. The serum NFκβ and IL-10 levels were measured after 3 weeks treated with MSC-WJ using the ELISA method. The statistical test used is an independent t-test. p < 0.05 was said to be statistically significant. RESULTS: From the research results obtained, serum levels of knee OA of rat knee OA treated with mesenchymal stem cell Wharton jelly are lower than serum NFκβ levels of knee OA of the rat that is not treated, but the difference in levels of NFκβ is not significant (p > 0.05). The serum IL-10 level of rat OA of knee treated with mesenchymal stem cell Wharton jelly was higher than the serum IL-10 level of rat OA of the knee that was not treated, difference in levels of IL-10, is significant (p < 0.05). CONCLUSION: This study concluded that MSC-WJ significantly decreased the serum NFκβ levels of OA rats and not significantly increased the serum IL-10 levels of OA rats.


Author(s):  
A. Singh ◽  
A. Dykeman ◽  
J. Jarrelf ◽  
D. C. Villeneuve

Hexachlorobenzene (HCB), a persistent and mobile organochlorine pesticide, occurs in environment. HCB has been shown to be present in human follicular fluid. An objective of the present report, which is part of a comprehensive study on reproductive toxicity of HCB, was to determine the cytologic effects of the compound on ovarian follicles in a primate model.Materials and Methods. Eight Cynomolgus monkeys were housed under controlled conditions at Animal facility of Health and Welfare, Ottawa. Animals were orally administered gelatin capsules containing HCB mixed with glucose in daily dosages of 0.0 or 10 mg/kg b.w. for 90 days; the former was the control group. On the menstrual period following completion of dosing, the monkeys underwent an induction cycle of superovulation. At necropsy, one-half of an ovary from each animal was diced into ca. 2- to 3-mm cubed specimens that were fixed by immersion in 2.5% glutaraldehyde in 0.1 M cacodylate buffer (pH 7.3). Subsequent procedures followed to obtain thin sections that were examined in a Hitachi H-7000 electron microscope have been described earlier.


2017 ◽  
Vol 68 (2) ◽  
pp. 323-327
Author(s):  
Cristian Levente Giuroiu ◽  
Maria Vataman ◽  
Gabriel Melian ◽  
Dragos Bularda ◽  
Ludmila Lozneanu ◽  
...  

The study aimed to assess the number, localization and distribution of interleukin 6 (IL-6) positive cells in healthy pulp, acute and chronic pulpitis. The study group included 48 patients aged between 18-72, treated in University of Medicine and Pharmacy Grigore T. Popa Iasi, Romania. The pulpectomy was performed on 42 patients diagnosed with acute and chronic pulpitis. The other 6 patients, without signs of dental caries or periodontal disease, were submitted to extractions of teeth for orthodontic purposes, with pulpectomy performed before extraction. The pulp samples were examined with optic microscope. The detection and assessment of IL-6 were performed using immunohistochemical technique. Data were statistically analysed using non-parametric tests. According to morphopathological criteria, 42.85% were classified as acute pulpitis and 57.14% as chronic pulpitis. The pulp samples in control group were not associated with IL-6 positive cells. The analysis of all samples with acute and chronic pulpitis identified 73.80% samples with IL-6 and 26.20% associated with the absence of IL-6. The highest frequency of IL-6 positive cells was recorded in rich-cell zone of crown dental pulp. The systemic distribution of IL-6 positive cells was mostly diffused without well-defined orientation. IL-6 release in acute and chronic pulpitis is significantly higher comparing with healthy pulp tissue.


2018 ◽  
Vol 69 (8) ◽  
pp. 2081-2088 ◽  
Author(s):  
Alin Alexandru Odor ◽  
Edwin Sever Bechir ◽  
Deborah Violant ◽  
Victoria Badea

Moderate and severe periodontitis represents a challenge in the non-surgical periodontal therapy. Due to the lack of evidence regarding the antimicrobial effectiveness of 940 nm diode laser in periodontal treatment, this study aimed to evaluate the antimicrobial effect of hydrogen peroxide (H2O2) photolysis performed with 940 nm diode laser in the treatment of moderate and severe periodontitis. Twenty-five patients with 100 teeth were selected for this pilot study. The test teeth were randomly assigned to one of the four treatment groups: Group 1: scaling and root planning (SRP) (control group); and the following experimental groups: Group 2: H2O2; Group 3: 940 nm diode laser therapy; Group 4: 940 nm diode laser therapy and H2O2. Clinical examinations, like probing depth (PD), clinical attachment level (CAL) and bleeding on probing (BOP) were performed before and after the treatment. The microbiological evaluation, effectuated before and after the treatment, included nine periodontal bacteria species and investigated by means of real-time PCR assay. The clinical and bacterial differences in the tested groups, was assessed between control group and the other three experimental groups, as well as between the experimental groups. The total bacteria load was reduced for all four studied groups. Group 4 (diode laser + H2O2) showed significant bacterial reduction of the major periodontal bacteria like Pg., Tf., Td., Pi., Pm., Fn (p[0.001) than the other 3 groups (p]0.001). Also the periodontal clinical parameters, like PD, CAL and BOP showed a significant reduction after the photolysis of H2O2 with the 940 nm diode laser (p[0.001). Differences between tested groups showed a significant beneficial results in regard to Group 4.It is suggested that the photoactivation of H2O2 with the 940 nm diode laser can be used successfully in adjunctive to the non-surgical periodontal treatment as a bactericidal tool.


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