Aijun Yang1,2,3, Yanzhu Lu1,2,3, Junchao Xing1,2,3, Zhilin Li1,2,3,4, Xiaolong Yin1,2,3, Ce Dou1,2,3, Shiwu Dong1,2,3,5, Fei Luo1,2,3, Zhao Xie1,2,3, Tianyong Hou1,2,3, Jianzhong Xu1,2,3. 1. Department of Orthopedics, National & Regional United Engineering Laboratory of Tissue Engineering, Southwest Hospital, the Third Military Medical University, Chongqing, China. 2. Center of Regenerative and Reconstructive Engineering Technology in Chongqing City, Chongqing, China. 3. Tissue Engineering Laboratory of Chongqing City, Chongqing, China. 4. Department of Spine, Lanzhou General Hospital, Lanzhou Command of CPLA, Lanzhou, China. 5. Department of Biomedical Materials Science, College of Biomedical Engineering, Third Military Medical University, Chongqing, China.
Abstract
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.
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.
Authors: Brandon A Coates; Jennifer A McKenzie; Evan G Buettmann; Xiaochen Liu; Paul M Gontarz; Bo Zhang; Matthew J Silva Journal: Bone Date: 2019-07-29 Impact factor: 4.398
Authors: Wei Qiao; Karen H M Wong; Jie Shen; Wenhao Wang; Jun Wu; Jinhua Li; Zhengjie Lin; Zetao Chen; Jukka P Matinlinna; Yufeng Zheng; Shuilin Wu; Xuanyong Liu; Keng Po Lai; Zhuofan Chen; Yun Wah Lam; Kenneth M C Cheung; Kelvin W K Yeung Journal: Nat Commun Date: 2021-05-17 Impact factor: 14.919