Cause and chondroprotective effects of prostaglandin E2 secretion during mesenchymal stromal cell chondrogenesis
Mesenchymal stromal cells (MSCs) that are promising for cartilage tissue engineering secrete high amounts of prostaglandin E2 (PGE2), an immunoactive mediator involved in endochondral bone development. This study aimed to identify drivers of PGE2 and its role in the inadvertent MSC misdifferentiatio...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2024-06-01
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| Series: | European Journal of Cell Biology |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0171933524000293 |
| _version_ | 1827207892251443200 |
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| author | Sven Schmidt Felicia A.M. Klampfleuthner Tobias Renkawitz Solvig Diederichs |
| author_facet | Sven Schmidt Felicia A.M. Klampfleuthner Tobias Renkawitz Solvig Diederichs |
| author_sort | Sven Schmidt |
| collection | DOAJ |
| description | Mesenchymal stromal cells (MSCs) that are promising for cartilage tissue engineering secrete high amounts of prostaglandin E2 (PGE2), an immunoactive mediator involved in endochondral bone development. This study aimed to identify drivers of PGE2 and its role in the inadvertent MSC misdifferentiation into hypertrophic chondrocytes. PGE2 release, which rose in the first three weeks of MSC chondrogenesis, was jointly stimulated by endogenous BMP, WNT, and hedgehog activity that supported the exogenous stimulation by TGF-β1 and insulin to overcome the PGE2 inhibition by dexamethasone. Experiments with PGE2 treatment or the inhibitor celecoxib or specific receptor antagonists demonstrated that PGE2, although driven by prohypertrophic signals, exerted broad autocrine antihypertrophic effects. This chondroprotective effect makes PGE2 not only a promising option for future combinatorial approaches to direct MSC tissue engineering approaches into chondral instead of endochondral development but could potentially have implications for the use of COX-2-selective inhibitors in osteoarthritis pain management. |
| first_indexed | 2024-04-24T10:04:49Z |
| format | Article |
| id | doaj.art-0b22007cc1e84674bca396163ffb215f |
| institution | Directory Open Access Journal |
| issn | 0171-9335 |
| language | English |
| last_indexed | 2025-03-21T12:47:17Z |
| publishDate | 2024-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | European Journal of Cell Biology |
| spelling | doaj.art-0b22007cc1e84674bca396163ffb215f2024-06-27T04:39:25ZengElsevierEuropean Journal of Cell Biology0171-93352024-06-011032151412Cause and chondroprotective effects of prostaglandin E2 secretion during mesenchymal stromal cell chondrogenesisSven Schmidt0Felicia A.M. Klampfleuthner1Tobias Renkawitz2Solvig Diederichs3Experimental Orthopaedics, Research Centre for Molecular and Regenerative Orthopaedics, Department of Orthopaedics, Heidelberg, GermanyExperimental Orthopaedics, Research Centre for Molecular and Regenerative Orthopaedics, Department of Orthopaedics, Heidelberg, GermanyResearch Centre for Molecular and Regenerative Orthopaedics, Department of Orthopaedics, Heidelberg University Hospital, Heidelberg, GermanyExperimental Orthopaedics, Research Centre for Molecular and Regenerative Orthopaedics, Department of Orthopaedics, Heidelberg, Germany; Correspondence to: Experimental Orthopaedics, Research Centre for Molecular and Regenerative Orthopaedics, Department for Orthopaedics, Heidelberg University Hospital, Schlierbacher Landstraße 200a, Heidelberg 69118, Germany.Mesenchymal stromal cells (MSCs) that are promising for cartilage tissue engineering secrete high amounts of prostaglandin E2 (PGE2), an immunoactive mediator involved in endochondral bone development. This study aimed to identify drivers of PGE2 and its role in the inadvertent MSC misdifferentiation into hypertrophic chondrocytes. PGE2 release, which rose in the first three weeks of MSC chondrogenesis, was jointly stimulated by endogenous BMP, WNT, and hedgehog activity that supported the exogenous stimulation by TGF-β1 and insulin to overcome the PGE2 inhibition by dexamethasone. Experiments with PGE2 treatment or the inhibitor celecoxib or specific receptor antagonists demonstrated that PGE2, although driven by prohypertrophic signals, exerted broad autocrine antihypertrophic effects. This chondroprotective effect makes PGE2 not only a promising option for future combinatorial approaches to direct MSC tissue engineering approaches into chondral instead of endochondral development but could potentially have implications for the use of COX-2-selective inhibitors in osteoarthritis pain management.http://www.sciencedirect.com/science/article/pii/S0171933524000293MSCsChondrogenesisPGE2COX-2EP2EP4 |
| spellingShingle | Sven Schmidt Felicia A.M. Klampfleuthner Tobias Renkawitz Solvig Diederichs Cause and chondroprotective effects of prostaglandin E2 secretion during mesenchymal stromal cell chondrogenesis European Journal of Cell Biology MSCs Chondrogenesis PGE2 COX-2 EP2 EP4 |
| title | Cause and chondroprotective effects of prostaglandin E2 secretion during mesenchymal stromal cell chondrogenesis |
| title_full | Cause and chondroprotective effects of prostaglandin E2 secretion during mesenchymal stromal cell chondrogenesis |
| title_fullStr | Cause and chondroprotective effects of prostaglandin E2 secretion during mesenchymal stromal cell chondrogenesis |
| title_full_unstemmed | Cause and chondroprotective effects of prostaglandin E2 secretion during mesenchymal stromal cell chondrogenesis |
| title_short | Cause and chondroprotective effects of prostaglandin E2 secretion during mesenchymal stromal cell chondrogenesis |
| title_sort | cause and chondroprotective effects of prostaglandin e2 secretion during mesenchymal stromal cell chondrogenesis |
| topic | MSCs Chondrogenesis PGE2 COX-2 EP2 EP4 |
| url | http://www.sciencedirect.com/science/article/pii/S0171933524000293 |
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