論文 - 詳細
| RRC ID | 51694 |
|---|---|
| 著者 | Caron MM, Emans PJ, Sanen K, Surtel DA, Cremers A, Ophelders D, van Rhijn LW, Welting TJ. |
| タイトル | The Role of Prostaglandins and COX-Enzymes in Chondrogenic Differentiation of ATDC5 Progenitor Cells. |
| ジャーナル | PLoS One |
| Abstract |
OBJECTIVES:NSAIDs are used to relieve pain and decrease inflammation by inhibition of cyclooxygenase (COX)-catalyzed prostaglandin (PG) synthesis. PGs are fatty acid mediators involved in cartilage homeostasis, however the action of their synthesizing COX-enzymes in cartilage differentiation is not well understood. In this study we hypothesized that COX-1 and COX-2 have differential roles in chondrogenic differentiation. METHODS:ATDC5 cells were differentiated in the presence of COX-1 (SC-560, Mofezolac) or COX-2 (NS398, Celecoxib) specific inhibitors. Specificity of the NSAIDs and inhibition of specific prostaglandin levels were determined by EIA. Prostaglandins were added during the differentiation process. Chondrogenic outcome was determined by gene- and protein expression analyses. RESULTS:Inhibition of COX-1 prevented Col2a1 and Col10a1 expression. Inhibition of COX-2 resulted in decreased Col10a1 expression, while Col2a1 remained unaffected. To explain this difference expression patterns of both COX-enzymes as well as specific prostaglandin concentrations were determined. Both COX-enzymes are upregulated during late chondrogenic differentiation, whereas only COX-2 is briefly expressed also early in differentiation. PGD2 and PGE2 followed the COX-2 expression pattern, whereas PGF2α and TXA2 levels remained low. Furthermore, COX inhibition resulted in decreased levels of all tested PGs, except for PGD2 and PGF2α in the COX-1 inhibited condition. Addition of PGE2 and PGF2α resulted in increased expression of chondrogenic markers, whereas TXA2 increased expression of hypertrophic markers. CONCLUSIONS:Our findings point towards a differential role for COX-enzymes and PG-production in chondrogenic differentiation of ATDC5 cells. Ongoing research is focusing on further elucidating the functional partition of cyclooxygenases and specific prostaglandin production. |
| 巻・号 | 11(4) |
| ページ | e0153162 |
| 公開日 | 2016-1-1 |
| DOI | 10.1371/journal.pone.0153162 |
| PII | PONE-D-16-05326 |
| PMID | 27050768 |
| PMC | PMC4822966 |
| MeSH | Animals Cartilage / chemistry* Cell Differentiation / physiology* Cell Line Cyclooxygenase 1 / metabolism* Cyclooxygenase 2 / metabolism* Mice Prostaglandins / physiology* Stem Cells / cytology* |
| IF | 2.74 |
| 引用数 | 8 |
| リソース情報 | |
| ヒト・動物細胞 | ATDC5(RCB0565) |