Immune and Repair Responses in Joint Tissues and Lymph Nodes after Knee Arthroplasty Surgery in Mice
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE174294 | GEO | 2022/05/01
REPOSITORIES: GEO
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Project description:OBJECTIVE: To analyze genome-wide changes in chondrocyte gene expression in a surgically induced model of early osteoarthritis (OA) in rats, to assess the similarity of this model to human OA, and to identify genes and mechanisms leading to OA pathogenesis. METHODS: OA was surgically induced in 5 rats by anterior cruciate ligament transection and partial medial meniscectomy. Sham surgery was performed in 5 additional animals, which were used as controls. Both groups underwent 4 weeks of forced mobilization, 3 times per week. RNA was extracted directly from articular chondrocytes in the OA (operated), contralateral, and sham-operated knees. Affymetrix GeneChip expression arrays were used to assess genome-wide changes in gene expression. Expression patterns of selected dysregulated genes, including Col2a1, Mmp13, Adamts5, Ctsc, Ptges, and Cxcr4, were validated by real-time polymerase chain reaction, immunofluorescence, or immunohistochemistry 2, 4, and 8 weeks after surgery. RESULTS: After normalization, comparison of OA and sham-operated samples showed 1,619 differentially expressed probe sets with changes in their levels of expression >/=1.5-fold, 722 with changes >/=2-fold, 135 with changes >/=4-fold, and 20 with changes of 8-fold. Dysregulated genes known to be involved in human OA included Mmp13, Adamts5, and Ptgs2, among others. Several dysregulated genes (e.g., Reln, Phex, and Ltbp2) had been identified in our earlier microarray study of hypertrophic chondrocyte differentiation. Other genes involved in cytokine and chemokine signaling, including Cxcr4 and Ccl2, were identified. Changes in gene expression were also observed in the contralateral knee, validating the sham operation as the appropriate control. CONCLUSION: Our results demonstrate that the animal model mimics gene expression changes seen in human OA, supporting the relevance of newly identified genes and pathways to early human OA. We propose new avenues for OA pathogenesis research and potential targets for novel OA treatments, including cathepsins and cytokine, chemokine, and growth factor signaling pathways, in addition to factors controlling the progression of chondrocyte differentiation. Experiment Overall Design: OA was surgically induced in 5 rats by anterior cruciate ligament transection and partial medial meniscectomy. Sham surgery was performed in 5 additional animals, which were used as controls. Both groups underwent 4 weeks of forced mobilization, 3 times per week. RNA was extracted directly from articular chondrocytes in the OA (operated), contralateral, and sham-operated knees, 28 days post-surgery. Affymetrix GeneChip expression arrays were used to assess genome-wide changes in gene expression.
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Project description:To analyze gene expression we isolated total mRNA from the core, periinfarct and contralateral cortex of 60 sprague-dawley rats after 24 hours or 3 days of permanent middle cerebral artery occlusion (pMCAo). Also ipsilateral and contralateral cortex was obtained from sham-operated and healthy animals. A total of 44 microarrays were performed with RNA pooled from 3 independent animals. For each experimental condition the total n number is of 12.
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Project description:Control rat lacrimal gland samples representing a normal unoperated, a sham, and paired contralateral controls. Experimental LG samples representing paired and unpaired contralateral controls. Paired contralateral control LGs represent LG from the same animal, one side was operated and the other side unoperated. Keywords: repeat sample
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Project description:We compared transcriptomic profiles of hepatic macrophages between sham operated rats, rats 3 days and 10 days after partial portal vein ligation (PPVL) surgery (n=3). The number of genes with a significant change was most numerous in Sham vs 3 days, followed by Sham vs 10 days and 3 days vs 10 days.
2019-01-01 | GSE117467 | GEO
Project description:To analyze gene expression we isolated total mRNA from the core, periinfarct and contralateral cortex of 60 sprague-dawley rats after 24 hours or 3 days of permanent middle cerebral artery occlusion (pMCAo). Also ipsilateral and contralateral cortex was obtained from sham-operated and healthy animals. A total of 44 microarrays were performed with RNA pooled from 3 independent animals. For each experimental condition the total n number is of 12. Microarray analysis of different areas of the rat brain (core, periinfarct and contralateral cortex) after 24h and 3days of permanent ischemia
2012-12-01 | E-GEOD-36010 | biostudies-arrayexpress
Project description:Mechanical Stimuli are arguably the most important aetiolgical factors in osteoarthritis (OA) development. Not only do we see disease arising from joints where the cartilage has sustained direct (e.g. intraarticular fracture) or indirect (e.g. meniscal injury) trauma, but mechanical factors are considered, at least partly, to explain the disease associations with aging and obesity. It is now well established that OA is not simply due to repeated wear and tear, leading to attrition of the articular surfaces, but that it requires activation of a number of inflammatory genes, which drive catabolic protease activity in the joint. These enzymes lead to breakdown of the major extracellular matrix components of cartilage, namely type II collagen, and the proteoglycan, aggrecan. Although it is unclear precisely which enzymes are responsible for matrix breakdown in human OA, Glasson et al showed that deletion of the aggrecan degrading enzyme, ADAMTS5 substantially protected the joint from surgically induced murine OA suggesting that it is a major aggrecanase in the mouse. This study was part of a wider study using the surgical model of murine OA, induced by destabilising the medial meniscus (DMM), to confirm the dependence of joint loading on disease progression and to reveal mechanosensitive genes within the joint which may be involved in the development of OA. Using this model we, and others, have shown that there is a robust degradation of articular cartilage over 4-12wks in male C57B/6 mice. We identified the gene response in joints early following induction of OA, prior to cartilage degradation, by extracting RNA from whole joints (after skin and muscle had been removed) 6hrs, 3 days and 7 days following sham and DMM surgery. An Affymetrix ST1 gene array was performed. Significantly regulated genes (>1.4 fold above naive and sham samples at any timepoint), or those considered to have a putative role in OA pathogenesis were selected for quantitative validation using Taqman low density microfluidic card arrays (TLDA). Gene expression in whole knee joints at 3 early time points post DMM surgery (before cartilage loss), 6hrs, 3days and 7days was examined. Two controls were identified, the first control consisted of age matched naïve mice that had undergone 15 minutes of anaesthesia but were not operated on (0hrs post surgery). The second control included mice which had undergone sham surgery (capsulotomy alone). For this RNA was taken at the same time points post surgery as DMM samples (6hrs, 3days and 7days). There were three biological replicates per condition (total of 21 samples). The right (ipsilateral) knee joint was taken and RNA extracted and processed for microarray analysis using the Affymetrix Mouse Gene 1.0 st v1 platform.
2011-01-13 | E-GEOD-26475 | biostudies-arrayexpress
Project description:This experiment was designed to study the alteration in expression of mRNA is kidney following recovery from transient acute renal failure. The model used was a 52 min. bilateral renal artery clamping, followed by reperfusion, which resulted in a transient loss of renal function, followed by a functional recovery. All tissue in this study was harvested 35 days post-surgery, when renal function was restored, and renal structure largelyy normal. For controls, sham-operated animals were used. An N of 6 post-ischemia reperfusion animals were used with 6 sham-operated controls. For hybridization studies, RNA from one of six post-ischemic acute renal failure animals were compared with with RNA from kidney of six sham-operated control animals. Each ARF vs. sham-operated comparison was performed twice, alternating the cy3 and cy5 label between the two hybridizations for each pair. A second set of hybridizations was carried out using sham vs. sham hybridizations. This was done to get a quantitative analysis of the variation of the biological and microarry platform.
2010-06-10 | E-GEOD-1714 | biostudies-arrayexpress
Project description:Ischaemic preconditioning is a method of protecting tissue against ischaemia-reperfusion injury. It is an innate protective mechanism that increases a tissue's tolerance to prolonged ischaemia when it is first subjected to short burst of ischaemia and reperfusion. It is thought to provide this protection by increasing the tissue's tolerance to ischaemia, therby reducing oxidative stress, inflammation and apoptosis in the preconditioned tissue. We used microarrays to investigate the genomic response induced by ischaemic preconditioning in muscle biopsies taken from the operative leg of total knee arthroplasty patients in order to gain insight into the ischaemic preconditioning mechanism. Patients undergoing primary knee arthroplasty were randomised to control and treatment (ischaemic preconditioning) groups. Patients in the treatment group received a preconditioning stimulus immediately prior to surgery. The ischaemic preconditioning stimulus consisted of three five-minute periods of tourniquet insufflation on the lower operative limb, interrupted by five minute periods of reperfusion. All patients had a tourniquet applied to the lower limb after the administration of spinal anaesthesia, as per normal protocol for knee arthroplasty surgery. Muscle biopsies were taken from the quadriceps muscle of the operative knee at the immediate onset of surgery (T0) and at 1 hour into surgery (T1). Total RNA was extracted from biospies of four control and four treatment patients and hybridised to the Affymetrix Human U133 2.0 chip.
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