2. Academic Validation
  3. Implication of CXCR2-Src axis in the angiogenic and osteogenic effects of FP-TEB

Implication of CXCR2-Src axis in the angiogenic and osteogenic effects of FP-TEB

  • NPJ Regen Med. 2024 Sep 20;9(1):24. doi: 10.1038/s41536-024-00364-0.
Sihao He # 1 2 3,  Tianyong Hou # 1 2 3,  Jiangling Zhou 1 2 3,  Bo Yu 1 2 3,  Juan Cai 1 2 3,  Fei Luo 1 2 3,  Jianzhong Xu 4 5 6,  Junchao Xing 7 8 9
Affiliations

Affiliations

  • 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 Orthopedics, National & Regional United Engineering Laboratory of Tissue Engineering, Southwest Hospital, the Third Military Medical University, Chongqing, China. xjzslw@163.com.
  • 5 Center of Regenerative and Reconstructive Engineering Technology in Chongqing City, Chongqing, China. xjzslw@163.com.
  • 6 Tissue Engineering Laboratory of Chongqing City, Chongqing, China. xjzslw@163.com.
  • 7 Department of Orthopedics, National & Regional United Engineering Laboratory of Tissue Engineering, Southwest Hospital, the Third Military Medical University, Chongqing, China. 46327289@qq.com.
  • 8 Center of Regenerative and Reconstructive Engineering Technology in Chongqing City, Chongqing, China. 46327289@qq.com.
  • 9 Tissue Engineering Laboratory of Chongqing City, Chongqing, China. 46327289@qq.com.
  • # Contributed equally.
PMID: 39304660 DOI: 10.1038/s41536-024-00364-0
Abstract

Application of tissue-engineered bones (TEBs) is hindered by challenges associated with incorporated viable cells. Previously, we employed freeze-drying techniques on TEBs to devitalize mesenchymal stem cells (MSCs) while preserving functional proteins, yielding functional proteins-based TEBs (FP-TEBs). Here, we aimed to elucidate their in vivo angiogenic and osteogenic capabilities and the mechanisms. qPCR arrays were employed to evaluate chemokines and receptors governing EC migration. Identified C-X-C chemokine receptors (CXCRs) were substantiated using shRNAs, and the pivotal role of CXCR2 was validated via conditional knockout mice. Finally, signaling molecules downstream of CXCR2 were identified. Additionally, Src, MAP4K4, and p38 MAPK were identified indispensable for CXCR2 function. Further investigations revealed that regulation of p38 MAPK by Src was mediated by MAP4K4. In conclusion, FP-TEBs promoted EC migration, angiogenesis, and osteogenesis via the CXCR2-Src-Map4k4-p38 MAPK axis.

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