IL-8 Enhances Therapeutic Effects of BMSCs on Bone Regeneration via CXCR2-Mediated PI3k/Akt Signaling Pathway

• Published in: Cellular physiology and biochemistry Vol. 48; no. 1; pp. 361 - 370
• Main Authors: Yang, Aijun, Lu, Yanzhu, Xing, Junchao, Li, Zhilin, Yin, Xiaolong, Dou, Ce, Dong, Shiwu, Luo, Fei, Xie, Zhao, Hou, Tianyong, Xu, Jianzhong
• Format: Journal Article
• Language: English
• Published: Basel, Switzerland S. Karger AG 01.01.2018; Cell Physiol Biochem Press GmbH & Co KG
• Subjects: Akt; Angiogenesis; Animals; Bone and Bones - pathology; Bone and Bones - physiology; Bone marrow; Bone Marrow Cells - cytology; Bone marrow mesenchymal stem cells (BMSCs); Bone Regeneration - drug effects; Cell Differentiation - drug effects; Cells, Cultured; Chondrogenesis - drug effects; Collagen Type II - metabolism; CXCR2; Cytokines; Growth factors; Heterocyclic Compounds, 3-Ring - pharmacology; Humans; Interleukin-8 (IL-8); Interleukin-8 - genetics; Interleukin-8 - metabolism; Interleukin-8 - pharmacology; Male; Mesenchymal Stem Cells - cytology; Mesenchymal Stem Cells - metabolism; Mice; Original Paper; Phenylurea Compounds - pharmacology; Phosphatidylinositol 3-Kinases - antagonists & inhibitors; Phosphatidylinositol 3-Kinases - metabolism; PI3k; Proteins; Proto-Oncogene Proteins c-akt - antagonists & inhibitors; Proto-Oncogene Proteins c-akt - metabolism; Receptors, Interleukin-8B - antagonists & inhibitors; Receptors, Interleukin-8B - metabolism; Signal Transduction - drug effects; Stem cells; Tissue engineered bone (TEB); Tissue Engineering; Transcription factors; Transplants & implants; Umbilical cord; United States > US; Interleukin-8 (IL-8); Akt; Tissue engineered bone (TEB); PI3k; Bone marrow mesenchymal stem cells (BMSCs); CXCR2
• ISSN: 1015-8987; 1421-9778
• DOI: 10.1159/000491742

Background/Aims: Tissue engineering bone transplantation with bone marrow mesenchymal stem cells (BMSCs) is an effective technology to treat massive bone loss, while molecular regulation of the bone regeneration processes remains poorly understood. Here, we aimed to assess the role of interleukin-8 (IL-8) in the recruitment of host cells by seeded BMSCs and in the bone regeneration. Methods: A transwell assay was performed to examine the role of IL-8/CXCR1/CXCR2/PI3k/Akt on the migration potential of hBMSCs. The in vitro chondrogenic differentiation of hBMSCs was assessed by examination of 2 chondrogenic markers, Sox9 and type 2 collagen (COL2). mBMSCs were used in tissue engineered bone (TEB) with/without IL-8 implanted into bone defect area with CXCR2 or Akt inhibitors. Density and Masson staining of the regenerated bone were assessed. The chondrogenesis was assessed by expression levels of associated proteins, Sox9 and COL2, by RT-qPCR and by immunohistochemistry. Results: IL-8 may trigger in vitro migration of hBMSCs via CXCR2-mediated PI3k/Akt signaling pathway. IL-8 enhances osteogenesis in the TEB-implanted bone defect in mice. IL-8 induces chondrogenic differentiation of hBMSCs via CXCR2-mediated PI3k/Akt signaling pathway in vitro and in vivo. Conclusions: IL-8 enhances therapeutic effects of MSCs on bone regeneration via CXCR2-mediated PI3k/Akt signaling pathway.