Synergetic Support of Cartilage Homeostasis via Coupled Thermal-Pressure Stimuli: A Transcriptomic Study in Human Cartilage Explants
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ABSTRACT:
PROVIDER: PRJNA1014403 | ENA |
REPOSITORIES: ENA
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Project description:During daily activities, cartilage encounters complex biophysical cues upon loading. Foremost among these is the coupled stimulation of hydrostatic pressure (HP) and loading-induced temperature increase (T), which encompasses both mechanical and thermal aspects of biophysical stimulations in cartilage. While prior research on this subject has been initiated in our laboratory, the detailed mechanisms of combined HP-T effects on chondrocytes in their natural environment remain largely unexplored. Using a custom bioreactor, we applied both isolated and combined HP-T stimuli to cartilage explants obtained from a non-inflammatory adolescent knee joint. Tissue and cellular responses were evaluated through histochemical staining and transcriptomic analyses, employing bulk RNA-sequencing complemented with signaling enrichment analyses. Our findings reveal that the thermal component of the coupled HP-T stimulation predominantly regulates the chondrocytes' transcriptional profile during the stimulation period. When coupled with HP stimulation, a peak in chondroinduction was observed. This coupling process notably boosted chondroprotection in a synergistic manner, as demonstrated by the corresponding enhanced negative regulation of apoptotic processes and increased levels of Heat Shock Protein 70 (HSPA). Our study suggests that the upregulation in protein translation and processing, triggered by thermal stimulation, may serve as an adaptive mechanism in chondrocytes to mechanical simulations, thereby contributing to the observed synergy during the coupling of these two biophysical stimuli. The results highlight the potential of integrating thermal stimulation, a natural accompanying process during cartilage deformation, in tissue engineering, cell therapy or physiotherapy.
2023-12-01 | GSE242710 | GEO
Project description:Osteoarthritis (OA) is a joint condition associated with articular cartilage loss, low-grade synovitis and alterations in subchondral bone and periarticular tissues. In OA, the interest for mesenchymal stem cell (MSC)-EV therapeutic applications has increased. We have assessed the immunomodulary properties of adipose-derived MSCs (AD-MSCs) microvesicles (MV) and exosomes (EX) in interleukin (IL)-1β stimulated OA chondrocytes and cartilage explants and characterized them by mass spectrometry in order to uncover novel mediators in (AD-MSC)-EV immunomodulation.
2022-02-23 | PXD009077 | Pride
Project description:Background: Osteoarthritis is a highly prevalent joint degenerative disease for which therapeutic treatments are limited or invasive. Cell therapy based on mesenchymal stem/stromal cells (MSCs) is therefore seen as a promising approach for this disease, in both human and horses. Objective: As the regenerative potential of MSCs is mainly conferred by paracrine function, the goal of this study is to characterize the secretome of muscle-derived MSCs (mdMSCs) in an in vitro model of OA to evaluate the clinical interest of mdMSCs as cell therapy for joint diseases like osteoarthritis. Methods: An equine osteoarthritis model composed of cartilage explants exposed to pro-inflammatory cytokines was first developed. Then, the effects of mdMSC coculture on cartilage explant were studied by measuring the glycosaminoglycan release and the NO2- production. To identify the underlying molecular actors, SILAC-based secretome analyses were conducted, in the presence of serum. The relative abundance of highly sequenced proteins was finally confirmed by western blot. Results: Co-culture with muscle-derived MSCs decreases the cytokine-induced glycosaminoglycan release by cartilage explants, suggesting a protecting effect of mdMSCs. Among the 52 equine proteins sequenced in the co-culture medium, the abundance of decorin and matrix metalloproteinase 3 was modified, as confirmed by western blot analyses. Conclusions: These results suggest that muscle-derived MSCs could reduce the catabolic effect of TNF and IL-1 on cartilage explant by decreasing the secretion and activity of Matrix Metalloproteinase 3 and increasing the decorin secretion
2022-11-08 | PXD031924 | Pride
Project description:proteins secreted during 5 day culture of articular cartilage explants
2012-03-04 | PRD000359 | Pride
Project description:Articular cartilage explants were incubated with or without interleukin-1β for 25 days. Media samples collected at 3-day intervals were analysed by quantitative proteomics. Semi-tryptic COMP peptides containing novel neo-epitopes were identified and quantified in cell culture media from cartilage explants.
2018-01-05 | PXD004993 | Pride
Project description:Osteoarthritis (OA) is an age-related degenerative musculoskeletal disease characterised by loss of articular cartilage, synovitis, abnormal bone proliferation and subchondral bone sclerosis. Underlying OA pathogenesis is yet to be fully elucidated with no OA specific biomarkers in clinical use. Ex-vivo equine cartilage explants (n=5) were incubated in TNF-α/IL-1β supplemented culture media for 8 days, with media removed and replaced at 2, 5 and 8 days. Acetonitrile metabolite extractions of 8 day cartilage explants and media samples at all time points underwent 1D 1H nuclear magnetic resonance metabolomic analysis with media samples also undergoing mass spectrometry proteomic analysis. Within the cartilage, metabolites glucose and lysine were elevated following TNF-α/IL-1β treatment whilst adenosine, alanine, betaine, creatine, myo-inositol and uridine levels decreased. Within the culture media, four, four and six differentially abundant metabolites and 154, 138 and 72 differentially abundant proteins, with > 2 fold change, were identified for 1-2 day, 3-5 day and 6-8 day time points respectively. Nine potential novel OA neopeptides were elevated in treated media. Our novel study identified metabolites, proteins and extracellular matrix derived neopeptides which provides insightful information on OA pathogenesis, enabling potential translation for clinical markers and possible novel therapeutic targets.
2020-09-30 | MTBLS1495 | MetaboLights
Project description:Successfully replacing damaged cartilage with tissue-engineered constructs requires integration with the host tissue and could benefit from leveraging the native tissue's intrinsic healing capacity; however, efforts are limited by a poor understanding of how cartilage repairs minor defects. Here, we investigated the conditions that foster natural cartilage tissue repair to identify strategies that might be exploited to enhance the integration of engineered/ grafted cartilage with host tissue. We damaged porcine articular cartilage explants and using a combination of pulsed SILAC-based proteomics, ultrastructural imaging, and catabolic enzyme blocking strategies reveal that integration of damaged cartilage surfaces is not driven by neo-matrix synthesis, but rather local depletion of proteoglycans. ADAMTS4 expression and activity are upregulated in injured cartilage explants, but integration could be reduced by inhibiting metalloproteinase activity with TIMP3. These observations suggest that catabolic enzyme-mediated proteoglycan depletion likely allows existing collagen fibrils to undergo cross-linking, fibrillogenesis, or entanglement, driving integration. Catabolic enzymes are often considered pathophysiological markers of osteoarthritis. Our findings suggest that damage-induced upregulation of metalloproteinase activity may be a part of a healing response that tips towards tissue destruction under pathological conditions and in osteoarthritis, but could also be harnessed in tissue engineering strategies to mediate repair. Statement of significance: Cartilage tissue engineering strategies require graft integration with the surrounding tissue; however, how the native tissue repairs minor injuries is poorly understood. We applied pulsed SILACbased proteomics, ultrastructural imaging, and catabolic enzyme blocking strategies to a porcine cartilage explant model and found that integration of damaged cartilage surfaces is driven by catabolic enzyme-mediated local depletion of proteoglycans. Although catabolic enzymes have been implicated in cartilage destruction in osteoarthritis, our findings suggest that damage-induced upregulation of metalloproteinase activity may be a part of a healing response that tips towards tissue destruction under pathological conditions. They also suggest that this natural cartilage tissue repair process could be harnessed in tissue engineering strategies to enhance the integration of engineered cartilage with host tissue.
2022-07-18 | PXD035246 | Pride
Project description:The current study aimed to confirm chondroprotective effects of the D2 inhibitor iopanoic acid (IOP) in an ex vivo aged human osteochondral explant model in which injurious mechanical stress is applied to inflict OA-like damage. This dataset contains RNA-seq (Illumina HiSeq X ten) of osteochondral explant cartilage from aged human patients that underwent a joint replacement surgery due to OA (N=10 donors; n=21 explants).
| EGAS00001006242 | EGA
Project description:RATIONALE: Shark cartilage extract may help shrink or slow the growth of colorectal cancer or breast cancer cells.
PURPOSE: Randomized phase III trial to determine the effectiveness of shark cartilage in treating patients who have advanced colorectal cancer or advanced breast cancer.
| 2006841 | ecrin-mdr-crc
Project description:Osteoarthritis (OA) is an age-related degenerative musculoskeletal disease characterised by loss of articular cartilage, synovitis, abnormal bone proliferation and subchondral bone sclerosis. The underlying pathogenesis of OA is yet to be fully elucidated with no OA specific biomarkers in clinical use. Nuclear magnetic resonance (NMR) spectroscopy and mass spectrometry (MS) allow identification of the global metabolome and proteome respectively. During this study, ex-vivo equine cartilage explants (n=5) were incubated in TNF-α/IL-1β supplemented culture media for 8 days, with media removed and replaced at 2, 5 and 8 days. Acetonitrile metabolite extractions of 8 day cartilage explants and media samples at all time points underwent 1H NMR metabolic analysis with media samples also undergoing MS proteomic analysis. Within the cartilage, metabolites glucose and lysine were elevated following TNF-α/IL-1β treatment whilst adenosine, alanine, betaine, creatine, myo-inositol and uridine levels decreased. Within the culture media, four, four and six metabolites were identified as being differentially abundant between control and treatment groups for 1-2 day, 3-5 day and 6-8 day time points respectively. Culture media proteomics identified 154, 138 and 72 proteins differentially abundant, with > 2 fold change, between control and treatment groups for 1-2 day, 3-5 day and 6-8 day time points respectively. Nine potential novel OA neopeptides were elevated in treated media. This is the first study to use a multi ‘omics’ approach to simultaneously investigate the metabolomic profile of ex-vivo cartilage and metabolomic/proteomic profiles of culture media using the TNF-α/IL-1β ex-vivo OA cartilage model. This study has identified a panel of metabolites, proteins and extracellular matrix derived neopeptides which are differentially abundant during an early phase of the OA model which may provide further information on underlying disease pathogenesis, allow potential translation for clinical markers and possible novel therapeutic targets.
2020-08-03 | PXD017153 | Pride