HMGB1 promotes cellular chemokine synthesis and potentiates mesenchymal stromal cell migration via Rap1 activation.
The migration of mesenchymal stem cells (MSCs) and osteogenic differentiation occupy an important role in fracture healing. High mobility group box 1 (HMGB1), a widely distributed inflammatory factor in fractures, has been confirmed to act as a chemoattractant to MSCs. To investigate the effect of HMGB1 on MSC migration and the underlying mechanism, the synthesis of MSC chemokines, and the consequent activation of signaling pathways following HMGB1 stimulation, were evaluated. A Quantibody® array was performed to determine which chemokines were secreted from MSCs with or without treatment with HMGB1. The results indicated differential chemokine synthesis by MSCs following treatment with HMGB1, including that of CCL4 and CCL13. In addition, the Ras‑associated protein‑1 (Rap1) signaling pathway was markedly activated in the HMGB1‑treated groups, suggesting that HMGB1 may enhance the migrational ability of MSCs via Rap1 activation. Furthermore, HMGB1 was able to promote the secretion of various chemokines derived from MSCs, which would, in turn, increase the mobility of MSCs. Taken together, these results provide a mechanistic basis for developing novel approaches to promote fracture healing.
Department of Orthopedics, The First People's Hospital of Xiaoshan, Hangzhou, Zhejiang 311200, P.R. China.
Feng
F
Lin
Department of Orthopedics, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310009, P.R. China.
Deting
D
Xue
Department of Orthopedics, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310009, P.R. China.
Tao
T
Xie
Department of Orthopedics, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310009, P.R. China.
Zhijun
Z
Pan
D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D018925:Chemokines / Q000096:biosynthesis*; D016207:Cytokines / Q000096:biosynthesis; D024243:HMGB1 Protein / Q000378:metabolism* / Q000494:pharmacology; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000187:drug effects / Q000378:metabolism*; D000089804:Shelterin Complex; D015398:Signal Transduction / Q000187:drug effects; D034501:Telomere-Binding Proteins / Q000378:metabolism*
D018925:Chemokines; D016207:Cytokines; D024243:HMGB1 Protein; D000089804:Shelterin Complex; C440809:TERF2IP protein, human; D034501:Telomere-Binding Proteins