Dickkopf1 Up-Regulation Induced by a High Concentration of Dexamethasone Promotes Rat Tendon Stem Cells to Differentiate Into Adipocytes
Background/Aims: Dexamethasone (Dex)-induced spontaneous tendon rupture and decreased self-repair capability is very common in clinical practice. The metaplasia of adipose tissue in the ruptured tendon indicates that Dex may induce tendon stem cells (TSCs) to differentiate into adipocytes, but the m...
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| Format: | Article |
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Cell Physiol Biochem Press GmbH & Co KG
2015-11-01
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| Series: | Cellular Physiology and Biochemistry |
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| Online Access: | http://www.karger.com/Article/FullText/438538 |
| _version_ | 1818489454576271360 |
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| author | Wan Chen Hong Tang Xiangzhou Liu Mei Zhou Jiqiang Zhang Kanglai Tang |
| author_facet | Wan Chen Hong Tang Xiangzhou Liu Mei Zhou Jiqiang Zhang Kanglai Tang |
| author_sort | Wan Chen |
| collection | DOAJ |
| description | Background/Aims: Dexamethasone (Dex)-induced spontaneous tendon rupture and decreased self-repair capability is very common in clinical practice. The metaplasia of adipose tissue in the ruptured tendon indicates that Dex may induce tendon stem cells (TSCs) to differentiate into adipocytes, but the mechanism remains unclear. In the present study, we used in vitro methods to investigate the effects of Dex on rat TSC differentiation and the molecular mechanisms underlying this process. Methods: First, we used qPCR and Western blotting to detect the expression of the adipogenic differentiation markers aP2 and C/EBPα after treating the TSCs with Dex. Oil red staining was used to confirm that high concentration Dex promoted adipogenic differentiation of rat TSCs. Next, we used qPCR and Western blotting to detect the effect of a high concentration of dexamethasone on molecules related to the canonical WNT/β-catenin pathway in TSCs. Results: Treating rat TSCs with Dex promoted the synthesis of the inhibitory molecule dickkopf1 (DKK1) at the mRNA and protein levels. Western blotting results further showed that Dex downregulated the cellular signaling molecule phosphorylated glycogen synthase kinase-3β (P-GSK-3 β (ser9)), upregulated P-GSK-3β (tyr216), and downregulated the pivotal signaling molecule β-catenin. Furthermore, DKK1 knockdown attenuated Dex-induced inhibition of the canonical WNT/β-catenin pathway and of the adipogenic differentiation of TSCs. Lithium chloride (LiCl, a GSK-3β inhibitor) reduced Dex-induced inhibition of the classical WNT/β-catenin pathway in TSCs and of the differentiation of TSCs to adipocytes. Conclusion: In conclusion, by upregulating DKK1 expression, reducing the level of P-GSK-3β (ser9), and increasing the level of P-GSK-3β (tyr216), Dex causes the degradation of β-catenin, the central molecule of the classical WNT pathway, thereby inducing rat TSCs to differentiate into adipocytes. |
| first_indexed | 2024-12-10T17:03:57Z |
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| id | doaj.art-cd1c9b1cfd7e4f39a989cefb28af7644 |
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| issn | 1015-8987 1421-9778 |
| language | English |
| last_indexed | 2024-12-10T17:03:57Z |
| publishDate | 2015-11-01 |
| publisher | Cell Physiol Biochem Press GmbH & Co KG |
| record_format | Article |
| series | Cellular Physiology and Biochemistry |
| spelling | doaj.art-cd1c9b1cfd7e4f39a989cefb28af76442022-12-22T01:40:30ZengCell Physiol Biochem Press GmbH & Co KGCellular Physiology and Biochemistry1015-89871421-97782015-11-013751738174910.1159/000438538438538Dickkopf1 Up-Regulation Induced by a High Concentration of Dexamethasone Promotes Rat Tendon Stem Cells to Differentiate Into AdipocytesWan ChenHong TangXiangzhou LiuMei ZhouJiqiang ZhangKanglai TangBackground/Aims: Dexamethasone (Dex)-induced spontaneous tendon rupture and decreased self-repair capability is very common in clinical practice. The metaplasia of adipose tissue in the ruptured tendon indicates that Dex may induce tendon stem cells (TSCs) to differentiate into adipocytes, but the mechanism remains unclear. In the present study, we used in vitro methods to investigate the effects of Dex on rat TSC differentiation and the molecular mechanisms underlying this process. Methods: First, we used qPCR and Western blotting to detect the expression of the adipogenic differentiation markers aP2 and C/EBPα after treating the TSCs with Dex. Oil red staining was used to confirm that high concentration Dex promoted adipogenic differentiation of rat TSCs. Next, we used qPCR and Western blotting to detect the effect of a high concentration of dexamethasone on molecules related to the canonical WNT/β-catenin pathway in TSCs. Results: Treating rat TSCs with Dex promoted the synthesis of the inhibitory molecule dickkopf1 (DKK1) at the mRNA and protein levels. Western blotting results further showed that Dex downregulated the cellular signaling molecule phosphorylated glycogen synthase kinase-3β (P-GSK-3 β (ser9)), upregulated P-GSK-3β (tyr216), and downregulated the pivotal signaling molecule β-catenin. Furthermore, DKK1 knockdown attenuated Dex-induced inhibition of the canonical WNT/β-catenin pathway and of the adipogenic differentiation of TSCs. Lithium chloride (LiCl, a GSK-3β inhibitor) reduced Dex-induced inhibition of the classical WNT/β-catenin pathway in TSCs and of the differentiation of TSCs to adipocytes. Conclusion: In conclusion, by upregulating DKK1 expression, reducing the level of P-GSK-3β (ser9), and increasing the level of P-GSK-3β (tyr216), Dex causes the degradation of β-catenin, the central molecule of the classical WNT pathway, thereby inducing rat TSCs to differentiate into adipocytes.http://www.karger.com/Article/FullText/438538Tendon stem cellsAdipocytesDickkopf1GSK-3ββ-cateninDexamethasone |
| spellingShingle | Wan Chen Hong Tang Xiangzhou Liu Mei Zhou Jiqiang Zhang Kanglai Tang Dickkopf1 Up-Regulation Induced by a High Concentration of Dexamethasone Promotes Rat Tendon Stem Cells to Differentiate Into Adipocytes Cellular Physiology and Biochemistry Tendon stem cells Adipocytes Dickkopf1 GSK-3β β-catenin Dexamethasone |
| title | Dickkopf1 Up-Regulation Induced by a High Concentration of Dexamethasone Promotes Rat Tendon Stem Cells to Differentiate Into Adipocytes |
| title_full | Dickkopf1 Up-Regulation Induced by a High Concentration of Dexamethasone Promotes Rat Tendon Stem Cells to Differentiate Into Adipocytes |
| title_fullStr | Dickkopf1 Up-Regulation Induced by a High Concentration of Dexamethasone Promotes Rat Tendon Stem Cells to Differentiate Into Adipocytes |
| title_full_unstemmed | Dickkopf1 Up-Regulation Induced by a High Concentration of Dexamethasone Promotes Rat Tendon Stem Cells to Differentiate Into Adipocytes |
| title_short | Dickkopf1 Up-Regulation Induced by a High Concentration of Dexamethasone Promotes Rat Tendon Stem Cells to Differentiate Into Adipocytes |
| title_sort | dickkopf1 up regulation induced by a high concentration of dexamethasone promotes rat tendon stem cells to differentiate into adipocytes |
| topic | Tendon stem cells Adipocytes Dickkopf1 GSK-3β β-catenin Dexamethasone |
| url | http://www.karger.com/Article/FullText/438538 |
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