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

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.