DKK-1 Is Underexpressed in Mesenchymal Stem Cells from Patients with Ankylosing Spondylitis and Further Downregulated by IL-17
Dickkopf-1 (Dkk-1) is a key regulator of bone remodeling in spondyloarthropathies. Nevertheless, data regarding its expression in cells of pathophysiologic relevance, such as mesenchymal stem cells (MSCs), are lacking. Herein, we aimed to address DKK1 gene expression and Wnt pathway activation in MS...
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MDPI AG
2022-06-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/23/12/6660 |
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| author | Dimitrios Daoussis Anastasia Kanellou Elias Panagiotopoulos Dionysios Papachristou |
| author_facet | Dimitrios Daoussis Anastasia Kanellou Elias Panagiotopoulos Dionysios Papachristou |
| author_sort | Dimitrios Daoussis |
| collection | DOAJ |
| description | Dickkopf-1 (Dkk-1) is a key regulator of bone remodeling in spondyloarthropathies. Nevertheless, data regarding its expression in cells of pathophysiologic relevance, such as mesenchymal stem cells (MSCs), are lacking. Herein, we aimed to address DKK1 gene expression and Wnt pathway activation in MSCs from patients with ankylosing spondylitis (AS) and explore the effect of IL-17 on MSCs with respect to DKK-1 expression and Wnt pathway activation. Primary MSCs were isolated from the bone marrow of the femoral head of two patients with AS and two healthy controls undergoing orthopedic surgery. MSCs were cultured for 7 days in expansion medium and for 21 days in osteogenic medium in the presence or absence of IL-17A. Gene expression of DKK-1 and osteoblastic markers was determined by RT-PCR. Alkaline phosphatase activity, alizarin red and Van Kossa staining were used to assess osteoblastic function and mineralization capacity. DKK-1 was significantly downregulated in MSCs and osteoblasts from patients with AS compared to controls. Moreover, MSCs and osteoblasts from AS patients displayed increased Wnt pathway activation and enhanced osteoblastic activity, as indicated by increased expression of osteoblast marker genes and alkaline phosphatase activity. IL-17 downregulated DKK-1 expression and increased osteoblastic activity and mineralization capacity. DKK-1 is underexpressed in MSCs from AS patients compared to controls, whereas IL-17 has an inhibitory effect on DKK-1 expression and stimulates osteoblastic function. These data may have pathogenetic and clinical implications in AS. |
| first_indexed | 2024-03-09T23:34:23Z |
| format | Article |
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| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T23:34:23Z |
| publishDate | 2022-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-af2137a1b6ca4a1c9701ce8b6add6f9d2023-11-23T17:04:37ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-06-012312666010.3390/ijms23126660DKK-1 Is Underexpressed in Mesenchymal Stem Cells from Patients with Ankylosing Spondylitis and Further Downregulated by IL-17Dimitrios Daoussis0Anastasia Kanellou1Elias Panagiotopoulos2Dionysios Papachristou3Department of Rheumatology, University of Patras Medical School, Patras University Hospital, 26504 Patras, GreeceLaboratory of Bone and Soft Tissue Studies, Department of Anatomy-Histology-Embryology, University of Patras Medical School, 26504 Patras, GreeceDepartment of Orthopedics, University of Patras Medical School, Patras University Hospital, 26504 Patras, GreeceLaboratory of Bone and Soft Tissue Studies, Department of Anatomy-Histology-Embryology, University of Patras Medical School, 26504 Patras, GreeceDickkopf-1 (Dkk-1) is a key regulator of bone remodeling in spondyloarthropathies. Nevertheless, data regarding its expression in cells of pathophysiologic relevance, such as mesenchymal stem cells (MSCs), are lacking. Herein, we aimed to address DKK1 gene expression and Wnt pathway activation in MSCs from patients with ankylosing spondylitis (AS) and explore the effect of IL-17 on MSCs with respect to DKK-1 expression and Wnt pathway activation. Primary MSCs were isolated from the bone marrow of the femoral head of two patients with AS and two healthy controls undergoing orthopedic surgery. MSCs were cultured for 7 days in expansion medium and for 21 days in osteogenic medium in the presence or absence of IL-17A. Gene expression of DKK-1 and osteoblastic markers was determined by RT-PCR. Alkaline phosphatase activity, alizarin red and Van Kossa staining were used to assess osteoblastic function and mineralization capacity. DKK-1 was significantly downregulated in MSCs and osteoblasts from patients with AS compared to controls. Moreover, MSCs and osteoblasts from AS patients displayed increased Wnt pathway activation and enhanced osteoblastic activity, as indicated by increased expression of osteoblast marker genes and alkaline phosphatase activity. IL-17 downregulated DKK-1 expression and increased osteoblastic activity and mineralization capacity. DKK-1 is underexpressed in MSCs from AS patients compared to controls, whereas IL-17 has an inhibitory effect on DKK-1 expression and stimulates osteoblastic function. These data may have pathogenetic and clinical implications in AS.https://www.mdpi.com/1422-0067/23/12/6660ankylosing spondylitisnew bone formationDickkopf-1Dkk-1IL-17osteoblastogenesis |
| spellingShingle | Dimitrios Daoussis Anastasia Kanellou Elias Panagiotopoulos Dionysios Papachristou DKK-1 Is Underexpressed in Mesenchymal Stem Cells from Patients with Ankylosing Spondylitis and Further Downregulated by IL-17 International Journal of Molecular Sciences ankylosing spondylitis new bone formation Dickkopf-1 Dkk-1 IL-17 osteoblastogenesis |
| title | DKK-1 Is Underexpressed in Mesenchymal Stem Cells from Patients with Ankylosing Spondylitis and Further Downregulated by IL-17 |
| title_full | DKK-1 Is Underexpressed in Mesenchymal Stem Cells from Patients with Ankylosing Spondylitis and Further Downregulated by IL-17 |
| title_fullStr | DKK-1 Is Underexpressed in Mesenchymal Stem Cells from Patients with Ankylosing Spondylitis and Further Downregulated by IL-17 |
| title_full_unstemmed | DKK-1 Is Underexpressed in Mesenchymal Stem Cells from Patients with Ankylosing Spondylitis and Further Downregulated by IL-17 |
| title_short | DKK-1 Is Underexpressed in Mesenchymal Stem Cells from Patients with Ankylosing Spondylitis and Further Downregulated by IL-17 |
| title_sort | dkk 1 is underexpressed in mesenchymal stem cells from patients with ankylosing spondylitis and further downregulated by il 17 |
| topic | ankylosing spondylitis new bone formation Dickkopf-1 Dkk-1 IL-17 osteoblastogenesis |
| url | https://www.mdpi.com/1422-0067/23/12/6660 |
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