Osteoarthritis and Cartilage Regeneration: Focus on Pathophysiology and Molecular Mechanisms

Grässel, Susanne; Aszódi, Attila

doi:10.3390/ijms20246156

Cited by 28 publications

(20 citation statements)

References 43 publications

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“…Growth and molecular function proteins. Growth and molecular function-related proteins not only play important roles in cell and tissue growth but are also important for cartilage regeneration related to OA (28,29) In the present study, we identified 4 and 114 proteins related to growth and molecular functions, respectively, and we confirmed that their expression levels were increased or decreased in the ICRS3 group compared with the ICRS1 group. Metallothionein-2 (MT2A; -log 1.00-fold), metallothionein-1X (MT1X; -log 1.32-fold), argininosuccinate synthase (ASS1; -log 1.32-fold), isoform 2 of N-acetlymuramoyl-L-alanine amidase (PGLYRP2; -log 1.74-fold) and CD59 glycoprotein (CD59; -log 1.74-fold) were increased in the ICRS3 group compared with the ICRS1 group.…”

Section: Icrs Gradesupporting

confidence: 74%

Quantitative proteomic analysis comparing grades ICRS1 and ICRS3 in patients with osteoarthritis

et al. 2021

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Osteoarthritis (OA), which is caused by joint damage, is the most common form of arthritis, affecting millions of people worldwide. This damage can accumulate over time, which is why aging is one of the main contributors to joint damage associated with OA. The OA-related proteins that have been reported to date have been identified by the comparative analysis of OA patients with normal controls, following surgical or pharmacological treatment. For the first time, the present study analyzed OA-related proteins in patients with OA according to the International Cartilage Repair Society (ICRS) scale. Changes in protein expression can be observed during the OA process. The present study demonstrated differential protein expression patterns in articular cartilage from ICRS1and ICRS3-graded OA patients. ICRS grade-matched OA knee samples from 12 OA patients, 6 ICRS grade 1 patients and 6 ICRS3 patients were subjected to proteomic analysis using the LTQ-Orbitrap mass spectrometry system. A total of 231 unique proteins were identified as expressed across the ICRS1 and ICRS3 OA patient groups. Relative differences in protein expression associated with the following classifications were observed: Biological adhesion, cell killing, cellular process, development process and molecular function. Although some of these proteins have been previously reported to be associated with rheumatoid arthritis, including cartilage oligomeric matrix protein, collagen types, angiogenin, complement C5 and CD59 glycoprotein, numerous additional proteins were newly identified, which may further help our understanding of disease pathogenesis. These findings suggested that these proteins may be used to develop novel therapeutic targets for OA.

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Section: Icrs Gradesupporting

confidence: 74%

Quantitative proteomic analysis comparing grades ICRS1 and ICRS3 in patients with osteoarthritis

et al. 2021

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“…OA is classified as a degenerative joint disease, affecting the whole joint with all its tissue components. Functional and structural changes occur in multiple joint tissues and result in damage and loss of cartilage and the remodeling of subchondral bone resulting in pain as the most disabling symptom for the patient ( Litwic et al, 2013 ; Grässel and Aszodi, 2019 ). OP is characterized by an imbalance of bone formation and resorption, thereby affecting the integration of bone density and quality.…”

Section: Introductionmentioning

confidence: 99%

Influence of Extracellular Vesicles Isolated From Osteoblasts of Patients With Cox-Arthrosis and/or Osteoporosis on Metabolism and Osteogenic Differentiation of BMSCs

Niedermair

Lukas

et al. 2020

Front. Bioeng. Biotechnol.

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Background: Studies with extracellular vesicles (EVs), including exosomes, isolated from mesenchymal stem cells (MSC) indicate benefits for the treatment of musculoskeletal pathologies as osteoarthritis (OA) and osteoporosis (OP). However, little is known about intercellular effects of EVs derived from pathologically altered cells that might influence the outcome by counteracting effects from “healthy” MSC derived EVs. We hypothesize, that EVs isolated from osteoblasts of patients with hip OA (coxarthrosis/CA), osteoporosis (OP), or a combination of both (CA/OP) might negatively affect metabolism and osteogenic differentiation of bone-marrow derived (B)MSCs.Methods: Osteoblasts, isolated from bone explants of CA, OP, and CA/OP patients, were compared regarding growth, viability, and osteogenic differentiation capacity. Structural features of bone explants were analyzed via μCT. EVs were isolated from supernatant of naïve BMSCs and CA, OP, and CA/OP osteoblasts (osteogenic culture for 35 days). BMSC cultures were stimulated with EVs and subsequently, cell metabolism, osteogenic marker gene expression, and osteogenic differentiation were analyzed.Results: Trabecular bone structure was different between the three groups with lowest number and highest separation in the CA/OP group. Viability and Alizarin red staining increased over culture time in CA/OP osteoblasts whereas growth of osteoblasts was comparable. Alizarin red staining was by trend higher in CA compared to OP osteoblasts after 35 days and ALP activity was higher after 28 and 35 days. Stimulation of BMSC cultures with CA, OP, and CA/OP EVs did not affect proliferation but increased caspase 3/7-activity compared to unstimulated BMSCs. BMSC viability was reduced after stimulation with CA and CA/OP EVs compared to unstimulated BMSCs or stimulation with OP EVs. ALP gene expression and activity were reduced in BMSCs after stimulation with CA, OP, and CA/OP EVs. Stimulation of BMSCs with CA EVs reduced Alizarin Red staining by trend.Conclusion: Stimulation of BMSCs with EVs isolated from CA, OP, and CA/OP osteoblasts had mostly catabolic effects on cell metabolism and osteogenic differentiation irrespective of donor pathology and reflect the impact of tissue microenvironment on cell metabolism. These catabolic effects are important for understanding differences in effects of EVs on target tissues/cells when harnessing them as therapeutic drugs.

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“…Each of the common osteoarthritis risk factors might instigate a different mechanistic pathway leading to osteoarthritis. A number of strati cations have been proposed on the basis of speci c pathological processes to classify different mechanistic subgroups, which include an increased in ammatory component, mechanical overload, metabolic alterations, and cell senescence [37]. Knowledge of the heterogeneity of OA would help better de ne potential treatment targets, improve the ability to select appropriate patients for future clinical interventions and adapt outcome measures to the situation [38].…”

Section: Identi Cation and Characterization Of Molecular Subgroupsmentioning

confidence: 99%

Identification of Key Regulators Responsible for Dysregulated Networks in Osteoarthritis by Large-Scale Expression Analysis

Song

Wan

Zhou

et al. 2020

Preprint

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Background: Osteoarthritis (OA) is a worldwide musculoskeletal disorder. However, disease-modifying therapies for OA are not available. Here, we aimed to characterize the molecular signatures of OA and to identify novel therapeutic targets and strategies to improve the treatment of OA.Methods: We collected genome-wide transcriptome data performed on 161 OA and 88 normal human cartilage or synovium tissues from 9 independent datasets. Differential gene expression analysis and functional enrichment were performed to identify genes and pathways that were dysregulated in OA. The computational drug repurposing method was used to uncover drugs that could be repurposed to treat OA.Results: We identified several pathways associated with the development of OA, such as extracellular matrix adhesion, inflammation, carbohydrate metabolism, and collagen organization. By protein-protein interaction (PPI) network analysis, we prioritized several hub genes, such as JUN, IL-6, VAMP8, and SOCS3. Moreover, we repurposed several FDA-approved drugs, such as cardiac glycosides, that could be used in the treatment of OA. Conclusions: We proposed that the hub genes we identified will play a role in cartilage homeostasis and could be important diagnostic and therapeutic targets. Drugs such as protein kinase inhibitors and cardiac glycosides could improve the treatment of OA.

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Osteoarthritis and Cartilage Regeneration: Focus on Pathophysiology and Molecular Mechanisms

Abstract: Osteoarthritis (OA) is a leading cause of disability and source of societal cost in older adults [...]

Cited by 28 publications

References 43 publications

Quantitative proteomic analysis comparing grades ICRS1 and ICRS3 in patients with osteoarthritis

Quantitative proteomic analysis comparing grades ICRS1 and ICRS3 in patients with osteoarthritis

Influence of Extracellular Vesicles Isolated From Osteoblasts of Patients With Cox-Arthrosis and/or Osteoporosis on Metabolism and Osteogenic Differentiation of BMSCs

Identification of Key Regulators Responsible for Dysregulated Networks in Osteoarthritis by Large-Scale Expression Analysis

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