Interleukin-17 Can Induce Osteoarthritis in Rabbit Knee Joints Similar to Hulth's Method.
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ABSTRACT:
SUBMITTER: Wang Z
PROVIDER: S-EPMC5549504 | biostudies-other | 2017
REPOSITORIES: biostudies-other
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Project description:BackgroundAnimal model of Knee Osteoarthritis (OA) is the primary testing methodology for studies on pathogenic mechanisms and therapies of human OA disease. Recent major modeling methods are divided into artificially induced and spontaneous. However, these methods have some disadvantages of slow progression, high cost and no correlation with the pathogenesis of OA.MethodsOur studies attempted to find a rapid, easy, and consistent with the natural pathological process of OA modeling method by intra-articular injection of stromal cell-derived factor 1 (SDF-1) in the rabbit knee. After induction we collected cartilage specimens from the medial femoral condyle to undergo macroscopic, histological, immunohistochemical, and biochemical evaluations. Meanwhile, compared with Hulth surgical method to evaluate its efficacy.ResultsMacroscopic observation and modified Mankin score of histological staining exhibited typical features of middle stage OA cartilage in SDF-1 injected groups. Immunohistochemically, the positive expression of interleukin-1 (IL-1) and tumor necrosis factor α(TNF-α) was earlier and higher in high dose SDF-1 group than the surgical group. The matrix metalloproteinases (MMPs) in synovial fluid and chondrocytes significantly increased, but type II collagen (COLII) and aggrecan (ACAN) protein expressions decreased in SDF-1 injected group following the extension of time and increase of SDF-1 concentration.ConclusionsOur data indicated intra-articular injection of SDF-1 (40μg/kg, three times for 12 weeks) can induce rabbit knee OA model successfully more rapidly and easily than traditional surgical modeling. The study provided a further option for the establishment of knee OA animal model.
| S-EPMC8019508 | biostudies-literature
Project description:Sclareol is a natural product initially isolated form Salvia sclarea which possesses immune-regulation and anti-inflammatory activities. However, the anti-osteoarthritic properties of sclareol have not been investigated. The present study is aimed at evaluating the potential effects of sclareol in interleukin-1? (IL-1?)-induced rabbit chondrocytes as well as an experimental rabbit knee osteoarthritis model induced by anterior cruciate ligament transection (ACLT). Cultured rabbit chondrocytes were pretreated with 1, 5 and 10 ?g/mL sclareol for 1 h and followed by stimulation of IL-1? (10 ng/mL) for 24 h. Gene expression of matrix metalloproteinase-1 (MMP-1), MMP-3, MMP-13, tissue inhibitors of metalloproteinase-1 (TIMP-1), inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX)-2 was determined by quantitative real-time polymerase chain reaction (qRT-PCR). MMP-3, TIMP-1, iNOS and COX-2 proteins were measured by Western blotting. Enzyme-linked immunosorbent assay (ELISA) was applied for nitric oxide (NO) and prostaglandin E2 (PGE2) assessment. For the in vivo study, rabbits received six weekly 0.3 mL sclareol (10 ?g/mL) intra-articular injections in the knees four weeks after ACLT surgery. Cartilage was harvested for measurement of MMP-1, MMP-3, MMP-13, TIMP-1, iNOS and COX-2 by qRT-PCR, while femoral condyles were used for histological evaluation. The in vitro results we obtained showed that sclareol inhibited the MMPs, iNOS and COX-2 expression on mRNA and protein levels, while increased the TIMP-1 expression. And over-production of NO and PGE2 was also suppressed. For the in vivo study, both qRT-PCR results and histological evaluation confirmed that sclareol ameliorated cartilage degradation. Hence, we speculated that sclareol may be an ideal approach for treating osteoarthritis.
| S-EPMC4440052 | biostudies-literature
Project description:BackgroundInterleukin-16 (IL-16), a pleiotropic cytokine, plays a fundamental role in inflammatory diseases. This study investigates the association between IL-16 polymorphisms and the risk of knee osteoarthritis (OA) in a Chinese population.MethodsThe IL-16 rs11556218, rs4072111, and rs4778889 polymorphisms were determined in 150 knee OA cases and 147 healthy controls through polymerase chain reaction-restriction fragment length polymorphism.ResultsThe results suggested that the variants in IL-16 gene rs11556218 site were associated with a decreased knee OA risk after adjusting for age, sex, BMI, and smoking and drinking status (TG vs. TT: OR, 0.69; 95% CI, 0.53-0.89; P = 0.006; GG vs. TT: OR, 0.64; 95% CI, 0.45-0.90; P = 0.042; dominant model: OR, 0.68; 95% CI, 0.29-0.87; P = 0.002; G vs. T allele: OR, 0.77; 95% CI, 0.66-0.90; P = 0.003). Similarly, subjects bearing the rs4072111 variant genotypes and alleles also had a lower susceptibility to knee OA compared with those bearing the wild-type (CT vs. CC: OR, 0.66; 95% CI, 0.53-0.83; P = 0.002; TT vs. CC: OR, 0.57; 95% CI, 0.40-0.82; P = 0.027; dominant model: OR, 0.65; 95%, CI 0.52-0.80; P <0.001; T vs. C allele: OR, 0.69; 95% CI, 0.58-0.81; P <0.001). Further, the C allele and the combined genotype (CC+CT) of rs4778889 were associated with a slightly decreased risk of knee OA. In addition, we found two high-risk haplotypes: TTT (OR, 3.70) and GCC (OR, 6.22). Finally, serum IL-16 levels of knee OA patients were significantly higher than those of controls (P = 0.001).ConclusionsDespite the small sample size, this is the first study suggesting IL-16 gene polymorphisms to be associated with the risk of knee OA.
| S-EPMC4425433 | biostudies-literature
Project description:To compare the MANKIN and OARSI cartilage histopathology assessment systems using human articular cartilage from a large number of donors across the adult age spectrum representing all levels of cartilage degradation.Human knees (n=125 from 65 donors; age range 23-92) were obtained from tissue banks. All cartilage surfaces were macroscopically graded. Osteochondral slabs representing the entire central regions of both femoral condyles, tibial plateaus, and the patella were processed for histology and Safranin O - Fast Green staining. Slides representing normal, aged, and osteoarthritis (OA) tissue were scanned and electronic images were scored online by five observers. Statistical analysis was performed for inter- and intra-observer variability, reproducibility and reliability.The inter-observer variability among five observers for the MANKIN system showed a similar good Intra-class correlation coefficient (ICC>0.81) as for the OARSI system (ICC>0.78). Repeat scoring by three of the five readers showed very good agreement (ICC>0.94). Both systems showed a high reproducibility among four of the five readers as indicated by the Spearman's rho value. For the MANKIN system, the surface represented by lesion depth was the parameter where all readers showed an excellent agreement. Other parameters such as cellularity, Safranin O staining intensity and tidemark had greater inter-reader disagreement.Both scoring systems were reliable but appeared too complex and time consuming for assessment of lesion severity, the major parameter determined in standardized scoring systems. To rapidly and reproducibly assess severity of cartilage degradation, we propose to develop a simplified system for lesion volume.
| S-EPMC3348372 | biostudies-literature
Project description:Osteoarthritis (OA) treatment is a major orthopedic challenge given that there is no ideal drug capable to reverse or stop the progression of the OA. In that regard, bisphosphonates have been proposed as potential disease-modifying drugs due to their possible chondroprotective effect related to obtaining a greater subchondral bone quality. However, their effectiveness in OA is still controversial and additionally, there is little evidence focused on their long-term effect in preclinical studies. The aim of this study was to evaluate the risedronate quantitative effect on articular and subchondral periarticular bone by histomorphometry, in an experimental rabbit model in an advanced stage of OA. Twenty-four adult New Zealand rabbits were included in the study. OA was surgically induced in one randomly chosen knee, using the contralateral as healthy control. Animals were divided into three groups (n = 8): placebo control group, sham surgery group and risedronate-treated group. After 24 weeks of treatment, cartilage and subchondral femorotibial pathology was evaluated by micro-computed tomography (micro-CT) and undecalcified histology. The research results demonstrated that the experimental animal model induced osteoarthritic changes in the operated joints, showing an increased cartilage thickness and fibrillation associated with underlying subchondral bone thinning and decreased trabecular bone quality. These changes were especially highlighted in the medial tibial compartments as a possible response to surgical instability. Regarding the trabecular analysis, significant correlations were found between 2D histomorphometry and 3D imaging micro-CT for the trabecular bone volume, trabecular separation, and the trabecular number. However, these associations were not strongly correlated, obtaining more precise measurements in the micro-CT analysis. Concerning the long-term risedronate treatment, it did not seem to have the capacity to reduce the osteoarthritic hypertrophic cartilage response and failed to diminish the superficial cartilage damage or prevent the trabecular bone loss. This study provides novel information about the quantitative effect of long-term risedronate use on synovial joint tissues.
| S-EPMC8100024 | biostudies-literature
Project description:The aims of this study were to explore the change of synovial fluid (SF) proteome in a knee osteoarthritis (KOA) rabbit model, and to provide a new target for the treatment of knee osteoarthritis at the proteomic level. Sixteen New Zealand rabbits were randomly and equally divided into two groups. Group A rabbits were subjected to right anterior cruciate ligament transection (ACLT), while group B rabbits were subjected to sham ACLT. Six weeks later, the proteomes of knee joint SF from group A and B rabbits were analyzed using a label-free quantitative proteomic analysis method. We extracted 944 relevant items from GO BlastGO2 for the 23 proteins differentially expressed between the two groups. The final annotation results were 23 protein sequences annotated by 462 GO items. According to the KEGG gene database of rabbit protein sequences, as well as annotation of the KO numbers of homologous/similar proteins to the relevant 64 KEGG pathways, we extracted the sequences of 16 significantly differently expressed proteins among the relevant 64 KEGG messages/metabolism pathways. These included adiponectin, pyruvate kinase, bisphosphoglycerate mutase, HtpG/heat shock proteins, hemoglobin subunit alpha-1 2, VCP (CDC48), 14-3-3 protein beta/theta/zeta, and ferritin heavy chain, whose levels were decreased in group A. The other proteins were fibrinogen alpha/beta/gamma chain, carboxylesterase 2, paraoxonase/arylesterase 1, apolipoprotein A-I, immunoglobulin heavy chain, and transferrin, whose levels were increased in group B. The identified differentially expressed proteins indicate the change of SF proteomic expression in KOA and may provide protein targets for treating this condition.
| S-EPMC6079142 | biostudies-literature
Project description:BACKGROUND:Interleukin-17 (IL-17), a pleiotropic cytokine, plays a significant role in the inflammatory diseases. By a pilot study with small population, IL-17 polymorphisms (IL-17A rs2275913 and IL-17F rs763780) showed a more potential risk factor in knee osteoarthritis (OA) in our recruited subjects. In the current study, the association between IL-17A rs2275913 and IL-17F rs763780and the risk of OA in a Chinese population is studied. METHODS:The IL-17A rs2275913 and IL-17F rs763780 polymorphisms were determined in 594 knee OA cases and 576 healthy controls, using polymerase chain reaction-restriction fragment length polymorphism assay. The relationship between genotype distribution and disease risk, as well as OA severity was analyzed by Chi-square test and multivariate logistic regression. RESULTS:The experimental results indicated that the polymorphism in IL-17 gene rs2275913 site were related to knee OA risk after the adjustment of BMI, sex, age, smoking and drinking status (AA vs. GG: odds ratio (OR), 1.411; 95% confidence interval (CI), 1.021-1.950; P?=?0.040; A allele vs. G allele: OR, 1.192; P?=?0.037; 95% CI, 1.012-1.404;). Similarly, subjects who are bearing the rs763780 variant genotypes (TC and CC) and C allele also had a higher susceptibility to knee OA compared with those who are bearing the TT genotype (TC vs. TT, OR: 1.312; P?=?0.039; 95% CI: 1.017-1.692; CC vs. TT, OR: 2.812, P?=?0.006, 95% CI: 1.338-5.909; C allele Vs. T allele, OR:1.413, P?=?0.002, 95% CI:1.141-1.751). In the meantime, one high-risk haplotypes, AC (OR was 7.22, P?<?0.01) was found. Both two polymorphisms do not correlated with OA severity based on Kellgren-Lawrence (K&L) scales. Finally, serum IL-17 levels of knee OA patients were greatly higher than those of controls (P?=?0.001). CONCLUSIONS:With the limited size sample, our study shows that IL-17 gene polymorphisms possibly related to the high-risk knee OA occurrence.
| S-EPMC6339292 | biostudies-literature
Project description:Interleukin-16 (IL-16) polymorphisms have been associated with various disease states, and its activity is dysregulated in synovial fibroblasts of individuals with rheumatoid arthritis. Here, the association between genetic polymorphisms in the gene encoding IL-16 and susceptibility to primary knee osteoarthritis was investigated in the Chinese Han population. The study included 228 unrelated patients, half of whom presented with primary knee osteoarthritis (OA); the remainder was healthy individuals. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was used to examine single nucleotide polymorphisms (SNPs) in IL16 in these patients. Statistical analysis was performed using the chi-square goodness-of-fit test, Hardy-Weinberg (H-W) equilibrium, linkage disequilibrium analysis, and logistic regression analysis. The genotype distributions of three IL16 SNPs, rs11556218, rs4778889, and rs4072111, were found to be in line with Hardy-Weinberg equilibrium criteria (P > 0.05). The single-factor logistic regression analysis showed that, compared with the T/T genotype, the T/G genotype decreased the risk of primary knee OA in rs11556218 (OR = 0.37, 95% CI = 0.18~0.82) and, compared with the C/C genotype, the C/T genotype increased the risk of primary knee OA in rs4072111 (OR = 1.83, 95% CI = 1.07~3.59). There was linkage disequilibrium between rs4778889 and rs11556218 (D= 0.592, r(2) = 0.213). Finally, logistic regression analysis showed that compared to haplotype TTC, the TTT haplotype was associated with an increased risk of primary knee OA (OR = 2.10, 95% CI = 1.09-4.98); however, the GCC haplotype was associated with a reduced risk of primary knee OA (OR = 0.36, 95% CI = 0.12-0.93). Thus, the genetic polymorphisms rs11556218, rs4778889, and rs4072111 in the gene encoding IL-16 are associated with primary knee OA in Chinese Han population.
| S-EPMC4358600 | biostudies-literature
Project description:Osteoarthritis (OA) of the hand is a common disease resulting in pain and impaired function. The pathogenesis of hand OA (HOA) is elusive and models to study it have not been described so far. Culture of chondrocytes is a model to study the development of cartilage degeneration, which is a hallmark of OA and well established in OA of the knee and hip. In the current study we investigated the feasibility human chondrocyte culture derived from proximal interphalangeal (PIP) finger joints of dissecting room cadavers. Index and middle fingers without signs of osteoarthritis were obtained from 30 cadavers using two different protocols. Hyaline cartilage from both articulating surfaces of the proximal interphalangeal (PIP) joint was harvested and digested in collagenase. Cultured chondrocytes were monitored for contamination, viability, and expression of chondrocyte specific genes. Chondrocytes derived from knee joints of the cadavers were cultured under identical conditions. Gene expression comparing chondrocytes from PIP and knee joints was carried out using Affymetrix GeneChip Human 2.0 ST arrays. The resulting differentially expressed genes were validated by real-time PCR and immunohistochemistry.Chondrocytes harvested up to 101 hours after death of the donors were viable. mRNA expression of collagen 2A1, aggrecan and Sox9 was significantly higher in chondrocytes as compared to cultured fibroblasts. Comparison of gene expression by chondrocytes from PIP and knee joints yielded 528 differentially expressed genes. Chondrocytes from the same joint region had a higher grade of similarity than chondrocytes of the same individual. These results were validated using real-time PCR and immunohistochemistry.We demonstrate for the first time a reliable method for culture of chondrocytes derived from PIP joints. PIP chondrocytes show a specific gene expression pattern and could be used as tool to study cartilage degeneration in HOA.
2016-01-01 | GSE68038 | GEO
Project description:Lesions of hyaline cartilage do not heal spontaneously, and represent a therapeutic challenge. In vitro engineering of articular cartilage using cells and biomaterials may prove to be the best solution. Patients with osteoarthritis (OA) may require tissue engineered cartilage therapy. Chondrocytes obtained from OA joints are thought to be involved in the disease process, and thus to be of insufficient quality to be used for repair strategies. Bone marrow (BM) derived mesenchymal stem cells (MSCs) from healthy donors may represent an alternative cell source. We have isolated chondrocytes from OA joints, performed cell culture expansion and tissue engineering of cartilage using a disc-shaped alginate scaffold and chondrogenic differentiation medium. We performed real-time reverse transcriptase quantitative PCR and fluorescence immunohistochemistry to evaluate mRNA and protein expression for a range of molecules involved in chondrogenesis and OA pathogenesis. Results were compared with those obtained by using BM-MSCs in an identical tissue engineering strategy. Finally the two populations were compared using genome-wide mRNA arrays. At three weeks of chondrogenic differentiation we found high and similar levels of hyaline cartilage-specific type II collagen and fibrocartilage-specific type I collagen mRNA and protein in discs containing OA and BM-MSC derived chondrocytes. Aggrecan, the dominant proteoglycan in hyaline cartilage, was more abundantly distributed in the OA chondrocyte extracellular matrix. OA chondrocytes expressed higher mRNA levels also of other hyaline extracellular matrix components. Surprisingly BM-MSC derived chondrocytes expressed higher mRNA levels of OA markers such as COL10A1, SSP1 (osteopontin), ALPL, BMP2, VEGFA, PTGES, IHH, and WNT genes, but lower levels of MMP3 and S100A4. Based on the results presented here, OA chondrocytes may be suitable for tissue engineering of articular cartilage.
| S-EPMC3650033 | biostudies-literature