MEK1/2 Inhibitor (GDC0623) Promotes Osteogenic Differentiation of Primary Osteoblasts Inhibited by IL-1β through the MEK-Erk1/2 and Jak/Stat3 Pathways
Objective. We evaluated the effects and mechanisms of GDC0623 on osteogenic differentiation of osteoblasts induced by IL-1β. Methodology. Osteoblasts were treated with 20 ng/ml IL-1β and 0.1 µM GDC0623. Cell proliferation levels were evaluated by the cell counting kit 8 (CCK8), EdU assay, and wester...
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| Format: | Article |
| Language: | English |
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Wiley
2021-01-01
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| Series: | International Journal of Endocrinology |
| Online Access: | http://dx.doi.org/10.1155/2021/5720145 |
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| author | Zeng-Qiao Zhang Xiao-Shen Hu Ye-Chen Lu Jun-Peng Zhang Wen-Yao Li Wei-Yang Zhang Wei Feng Dao-Fang Ding Jian-Guang Xu |
| author_facet | Zeng-Qiao Zhang Xiao-Shen Hu Ye-Chen Lu Jun-Peng Zhang Wen-Yao Li Wei-Yang Zhang Wei Feng Dao-Fang Ding Jian-Guang Xu |
| author_sort | Zeng-Qiao Zhang |
| collection | DOAJ |
| description | Objective. We evaluated the effects and mechanisms of GDC0623 on osteogenic differentiation of osteoblasts induced by IL-1β. Methodology. Osteoblasts were treated with 20 ng/ml IL-1β and 0.1 µM GDC0623. Cell proliferation levels were evaluated by the cell counting kit 8 (CCK8), EdU assay, and western blotting [proliferating cell nuclear antigen (PCNA) and Cyclin D1]. Osteoblasts were cultured in an osteogenic induction medium for 1–3 weeks after which their differentiations were assessed by alkaline phosphatase (ALP) staining, Alizarin Red staining, calcium concentration, immunocytochemistry staining, real-time quantitative PCR (RT-qPCR), and immunofluorescence staining. The osteogenesis-associated mechanisms were further evaluated by western blotting using appropriate antibodies. Results. Relative to the control group, IL-1β induced the rapid proliferation of osteoblasts and suppressed their osteogenic differentiations by upregulating the activities of MEK-Erk1/2 as well as Jak-Stat3 pathways and by elevating MMP13 and MMP9 levels. However, blocking of the MEK-Erk1/2 signaling pathway by GDC0623 treatment reversed these effects. Conclusion. Inhibition of Jak-Stat3 pathway by C188-9 downregulated the expression levels of MMP9 and MMP13, activated MEK-Erk1/2 pathway, and inhibited osteogenic differentiation. |
| format | Article |
| id | doaj-art-ecb4016f65984c60b05af74ddac7921c |
| institution | Kabale University |
| issn | 1687-8345 |
| language | English |
| publishDate | 2021-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | International Journal of Endocrinology |
| spelling | doaj-art-ecb4016f65984c60b05af74ddac7921c2025-02-03T05:47:00ZengWileyInternational Journal of Endocrinology1687-83452021-01-01202110.1155/2021/5720145MEK1/2 Inhibitor (GDC0623) Promotes Osteogenic Differentiation of Primary Osteoblasts Inhibited by IL-1β through the MEK-Erk1/2 and Jak/Stat3 PathwaysZeng-Qiao Zhang0Xiao-Shen Hu1Ye-Chen Lu2Jun-Peng Zhang3Wen-Yao Li4Wei-Yang Zhang5Wei Feng6Dao-Fang Ding7Jian-Guang Xu8School of Rehabilitation ScienceSchool of Health Preservation and RehabilitationSchool of Rehabilitation ScienceSchool of Rehabilitation ScienceSchool of Rehabilitation ScienceSchool of Sports Medicine and HealthSchool of Rehabilitation ScienceSchool of Rehabilitation ScienceSchool of Rehabilitation ScienceObjective. We evaluated the effects and mechanisms of GDC0623 on osteogenic differentiation of osteoblasts induced by IL-1β. Methodology. Osteoblasts were treated with 20 ng/ml IL-1β and 0.1 µM GDC0623. Cell proliferation levels were evaluated by the cell counting kit 8 (CCK8), EdU assay, and western blotting [proliferating cell nuclear antigen (PCNA) and Cyclin D1]. Osteoblasts were cultured in an osteogenic induction medium for 1–3 weeks after which their differentiations were assessed by alkaline phosphatase (ALP) staining, Alizarin Red staining, calcium concentration, immunocytochemistry staining, real-time quantitative PCR (RT-qPCR), and immunofluorescence staining. The osteogenesis-associated mechanisms were further evaluated by western blotting using appropriate antibodies. Results. Relative to the control group, IL-1β induced the rapid proliferation of osteoblasts and suppressed their osteogenic differentiations by upregulating the activities of MEK-Erk1/2 as well as Jak-Stat3 pathways and by elevating MMP13 and MMP9 levels. However, blocking of the MEK-Erk1/2 signaling pathway by GDC0623 treatment reversed these effects. Conclusion. Inhibition of Jak-Stat3 pathway by C188-9 downregulated the expression levels of MMP9 and MMP13, activated MEK-Erk1/2 pathway, and inhibited osteogenic differentiation.http://dx.doi.org/10.1155/2021/5720145 |
| spellingShingle | Zeng-Qiao Zhang Xiao-Shen Hu Ye-Chen Lu Jun-Peng Zhang Wen-Yao Li Wei-Yang Zhang Wei Feng Dao-Fang Ding Jian-Guang Xu MEK1/2 Inhibitor (GDC0623) Promotes Osteogenic Differentiation of Primary Osteoblasts Inhibited by IL-1β through the MEK-Erk1/2 and Jak/Stat3 Pathways International Journal of Endocrinology |
| title | MEK1/2 Inhibitor (GDC0623) Promotes Osteogenic Differentiation of Primary Osteoblasts Inhibited by IL-1β through the MEK-Erk1/2 and Jak/Stat3 Pathways |
| title_full | MEK1/2 Inhibitor (GDC0623) Promotes Osteogenic Differentiation of Primary Osteoblasts Inhibited by IL-1β through the MEK-Erk1/2 and Jak/Stat3 Pathways |
| title_fullStr | MEK1/2 Inhibitor (GDC0623) Promotes Osteogenic Differentiation of Primary Osteoblasts Inhibited by IL-1β through the MEK-Erk1/2 and Jak/Stat3 Pathways |
| title_full_unstemmed | MEK1/2 Inhibitor (GDC0623) Promotes Osteogenic Differentiation of Primary Osteoblasts Inhibited by IL-1β through the MEK-Erk1/2 and Jak/Stat3 Pathways |
| title_short | MEK1/2 Inhibitor (GDC0623) Promotes Osteogenic Differentiation of Primary Osteoblasts Inhibited by IL-1β through the MEK-Erk1/2 and Jak/Stat3 Pathways |
| title_sort | mek1 2 inhibitor gdc0623 promotes osteogenic differentiation of primary osteoblasts inhibited by il 1β through the mek erk1 2 and jak stat3 pathways |
| url | http://dx.doi.org/10.1155/2021/5720145 |
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