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CCL2 promotes proliferation, migration and angiogenesis through the MAPK/ERK1/2/MMP9, PI3K/AKT, Wnt/β‑catenin signaling pathways in HUVECs

  • Authors:
    • Zhonghua Peng
    • He Pang
    • Hang Wu
    • Xin Peng
    • Qichao Tan
    • Sien Lin
    • Bo Wei
  • View Affiliations / Copyright

    Affiliations: Orthopedics Center, Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong 524001, P.R. China
    Copyright: © Peng et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 77
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    Published online on: December 27, 2022
       https://doi.org/10.3892/etm.2022.11776
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Abstract

Severe bone trauma can lead to poor or delayed bone healing and nonunion. Bone regeneration is based on the interaction between osteogenesis and angiogenesis. Angiogenesis serves a unique role in the repair and remodeling of bone defects. Monocyte chemoattractant protein‑1, also known as CC motif ligand 2 (CCL2), is a member of the CC motif chemokine family and was the first human chemokine to be revealed to be an effective chemokine of monocytes. However, its underlying mechanism in angiogenesis of bone defect repair remains to be elucidated. Therefore, the present study investigated the detailed mechanism by which CCL2 promoted angiogenesis in bone defects based on cell and animal model experiments. In the present study, CCL2 promoted proliferation, migration and tube formation in human umbilical vein endothelial cells (HUVECs) in a concentration‑dependent manner. Western blot analysis revealed that treatment of HUVECs with CCL2 upregulated the protein expression levels of rho‑associated coiled‑coil‑containing protein kinase (Rock)1, Rock2, N‑cadherin, c‑Myc and VEGFR2. Furthermore, CCL2 promoted the expression of MAPK/ERK1/2/MMP9, PI3K/AKT and Wnt/β‑catenin signaling pathway‑related proteins, which also demonstrated that CCL2 promoted these functions in HUVECs. Immunohistochemical staining of Sprague Dawley rat femurs following bone defects revealed that VEGF expression was positive in the newly formed bone area in each group, while the expression area of VEGF in the CCL2 addition group was markedly increased. Therefore, CCL2 is a potential therapeutic approach for bone defect repair and reconstruction through the mechanism of angiogenesis‑osteogenesis coupling.
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Copy and paste a formatted citation
Spandidos Publications style
Peng Z, Pang H, Wu H, Peng X, Tan Q, Lin S and Wei B: CCL2 promotes proliferation, migration and angiogenesis through the MAPK/ERK1/2/MMP9, PI3K/AKT, Wnt/β‑catenin signaling pathways in HUVECs. Exp Ther Med 25: 77, 2023.
APA
Peng, Z., Pang, H., Wu, H., Peng, X., Tan, Q., Lin, S., & Wei, B. (2023). CCL2 promotes proliferation, migration and angiogenesis through the MAPK/ERK1/2/MMP9, PI3K/AKT, Wnt/β‑catenin signaling pathways in HUVECs. Experimental and Therapeutic Medicine, 25, 77. https://doi.org/10.3892/etm.2022.11776
MLA
Peng, Z., Pang, H., Wu, H., Peng, X., Tan, Q., Lin, S., Wei, B."CCL2 promotes proliferation, migration and angiogenesis through the MAPK/ERK1/2/MMP9, PI3K/AKT, Wnt/β‑catenin signaling pathways in HUVECs". Experimental and Therapeutic Medicine 25.2 (2023): 77.
Chicago
Peng, Z., Pang, H., Wu, H., Peng, X., Tan, Q., Lin, S., Wei, B."CCL2 promotes proliferation, migration and angiogenesis through the MAPK/ERK1/2/MMP9, PI3K/AKT, Wnt/β‑catenin signaling pathways in HUVECs". Experimental and Therapeutic Medicine 25, no. 2 (2023): 77. https://doi.org/10.3892/etm.2022.11776
Copy and paste a formatted citation
x
Spandidos Publications style
Peng Z, Pang H, Wu H, Peng X, Tan Q, Lin S and Wei B: CCL2 promotes proliferation, migration and angiogenesis through the MAPK/ERK1/2/MMP9, PI3K/AKT, Wnt/β‑catenin signaling pathways in HUVECs. Exp Ther Med 25: 77, 2023.
APA
Peng, Z., Pang, H., Wu, H., Peng, X., Tan, Q., Lin, S., & Wei, B. (2023). CCL2 promotes proliferation, migration and angiogenesis through the MAPK/ERK1/2/MMP9, PI3K/AKT, Wnt/β‑catenin signaling pathways in HUVECs. Experimental and Therapeutic Medicine, 25, 77. https://doi.org/10.3892/etm.2022.11776
MLA
Peng, Z., Pang, H., Wu, H., Peng, X., Tan, Q., Lin, S., Wei, B."CCL2 promotes proliferation, migration and angiogenesis through the MAPK/ERK1/2/MMP9, PI3K/AKT, Wnt/β‑catenin signaling pathways in HUVECs". Experimental and Therapeutic Medicine 25.2 (2023): 77.
Chicago
Peng, Z., Pang, H., Wu, H., Peng, X., Tan, Q., Lin, S., Wei, B."CCL2 promotes proliferation, migration and angiogenesis through the MAPK/ERK1/2/MMP9, PI3K/AKT, Wnt/β‑catenin signaling pathways in HUVECs". Experimental and Therapeutic Medicine 25, no. 2 (2023): 77. https://doi.org/10.3892/etm.2022.11776
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