Habip Karaturk, Zeynep Burcin Gonen, Recep Saraymen, Nur Seda Gokdemir, Hasan Salkin
{"title":"Effects of dental pulp-derived mesenchymal stem cell exosomes produced under hypoxia conditions on osteoarthritic chondrocytes.","authors":"Habip Karaturk, Zeynep Burcin Gonen, Recep Saraymen, Nur Seda Gokdemir, Hasan Salkin","doi":"10.1080/03008207.2025.2519064","DOIUrl":null,"url":null,"abstract":"<p><strong>Purpose: </strong>Osteoarthritis is a common cause of disability worldwide. Exosomes are extracellular vesicles and can exert paracrine and endocrine actions. DPSCs exosomes offer a new avenue of research that may elucidate various functions related to cell proliferation, differentiation, and immunomodulation. We hypothesized that DPSC exosomes produced under hypoxia-induced culture conditions may have an anti-inflammatory effect on osteoarthritic chondrocytes and may re-regulate the inflammatory response that is increased in osteoarthritis. We also hypothesized that the decreased glycosaminoglycan production in osteoarthritis may be re-induced by DPSC exosomes produced under hypoxia.</p><p><strong>Materials and methods: </strong>Exosomes were isolated from DPSCs under hypoxic (3% O<sub>2</sub>) and normoxic conditions (21% O<sub>2</sub>) separately and were applied to OA chondrocyte cells. Quantification, morphology and analysis of tetraspanin markers were performed to characterize the exosomes. After the OA chondrocytes were treated with exosomes for 48 hours, they were prepared for cell proliferation, apoptosis, viability, glycosaminoglycan tests, and inflammatory cytokine analysis.</p><p><strong>Results: </strong>Our results show that the pro-inflammatory cytokines were significantly suppressed in osteoarthritic chondrocytes by DPSC exosomes produced under hypoxia (<i>p</i> < 0.05). Exosomes of DPSCs grown in a hypoxia environment dramatically increase the amount of GAG in OA chondrocytes, giving clues that they can be used in cartilage regeneration (<i>p</i> < 0.001).</p><p><strong>Conclusion: </strong>Considering that OA is associated with inflammatory components, DPSC exosome produced under hypoxic conditions prevents the formation of proinflammatory cytokines in osteoarthritic chondrocytes and shows therapeutic effects on osteoarthritic chondrocytes. Our study provides the first evidence showing the efficacy of DPSC-derived exosomes produced under hypoxia on osteoarthritic chondrocytes.</p>","PeriodicalId":10661,"journal":{"name":"Connective Tissue Research","volume":" ","pages":"1-13"},"PeriodicalIF":2.1000,"publicationDate":"2025-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Connective Tissue Research","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1080/03008207.2025.2519064","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"CELL BIOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Purpose: Osteoarthritis is a common cause of disability worldwide. Exosomes are extracellular vesicles and can exert paracrine and endocrine actions. DPSCs exosomes offer a new avenue of research that may elucidate various functions related to cell proliferation, differentiation, and immunomodulation. We hypothesized that DPSC exosomes produced under hypoxia-induced culture conditions may have an anti-inflammatory effect on osteoarthritic chondrocytes and may re-regulate the inflammatory response that is increased in osteoarthritis. We also hypothesized that the decreased glycosaminoglycan production in osteoarthritis may be re-induced by DPSC exosomes produced under hypoxia.
Materials and methods: Exosomes were isolated from DPSCs under hypoxic (3% O2) and normoxic conditions (21% O2) separately and were applied to OA chondrocyte cells. Quantification, morphology and analysis of tetraspanin markers were performed to characterize the exosomes. After the OA chondrocytes were treated with exosomes for 48 hours, they were prepared for cell proliferation, apoptosis, viability, glycosaminoglycan tests, and inflammatory cytokine analysis.
Results: Our results show that the pro-inflammatory cytokines were significantly suppressed in osteoarthritic chondrocytes by DPSC exosomes produced under hypoxia (p < 0.05). Exosomes of DPSCs grown in a hypoxia environment dramatically increase the amount of GAG in OA chondrocytes, giving clues that they can be used in cartilage regeneration (p < 0.001).
Conclusion: Considering that OA is associated with inflammatory components, DPSC exosome produced under hypoxic conditions prevents the formation of proinflammatory cytokines in osteoarthritic chondrocytes and shows therapeutic effects on osteoarthritic chondrocytes. Our study provides the first evidence showing the efficacy of DPSC-derived exosomes produced under hypoxia on osteoarthritic chondrocytes.
期刊介绍:
The aim of Connective Tissue Research is to present original and significant research in all basic areas of connective tissue and matrix biology.
The journal also provides topical reviews and, on occasion, the proceedings of conferences in areas of special interest at which original work is presented.
The journal supports an interdisciplinary approach; we present a variety of perspectives from different disciplines, including
Biochemistry
Cell and Molecular Biology
Immunology
Structural Biology
Biophysics
Biomechanics
Regenerative Medicine
The interests of the Editorial Board are to understand, mechanistically, the structure-function relationships in connective tissue extracellular matrix, and its associated cells, through interpretation of sophisticated experimentation using state-of-the-art technologies that include molecular genetics, imaging, immunology, biomechanics and tissue engineering.