Role of the HIF‑1α/SDF‑1/CXCR4 signaling axis in accelerated fracture healing after craniocerebral injury.

Abstract

The hypoxic state of the brain tissue surrounding craniocerebral injury induces an increase in the secretion of HIF-1α during the healing process. HIF-1α can promote mesenchymal stem cell (MSC) migration to ischemic and hypoxic sites by regulating the expression levels of molecules such as stromal cell-derived factor-1 (SDF-1) in the microenvironment. Stem cells express the SDF-1 receptor C-X-C chemokine receptor type 4 (CXCR4) and serve a key role in tissue repair, as well as a number of physiological and pathological processes. The present study aimed to determine the role of HIF-1α/SDF-1/CXCR4 signaling in the process of accelerated fracture healing during craniocerebral injury. Cultured MSCs underwent HIF-1α knockdown to elucidate its effect on the proliferative ability of MSCs, and the effect of SDF-1 in MSCs was investigated. It was also determined whether HIF-1α could promote osteogenesis via SDF-1/CXCR4 signaling and recruit MSCs. The results indicated that HIF-1α knockdown suppressed MSC proliferation in vitro, and SDF-1 promoted cell migration via binding to CXCR4. Furthermore, HIF-1α knockdown inhibited MSC migration via SDF-1/CXCR4 signaling. Considering the wide distribution and diversity of roles of SDF-1 and CXCR4, the present results may form a basis for the development of novel strategies for the treatment of craniocerebral injury.