Abstract
The effect of chronic intermittent hypobaric hypoxia (CIHH) on bone fracture healing is not elucidated. The present study aimed to investigate the role of CIHH on bone fracture healing and the mechanism. The Sprague-Dawley rats were randomly divided into the CIHH group and control group and monitored for 2, 4, or 8 weeks after femoral fracture surgery. Bone healing efficiency was significantly increased in the CIHH group as evidenced by higher high-density bone volume fractions, higher bone mineral density, higher maximum force, and higher stiffness. Histologically, the CIHH group exhibited superior bone formation, endochondral ossification, and angiogenic ability compared with the control group. The expression of HIF-1α and its downstream signaling proteins VEGF, SDF-1/CXCR4 axis were increased by the CIHH treatment. Moreover, the expression of RUNX2, osterix, and type I collagen in the callus tissues were also up-regulated in the CIHH group. In conclusion, our study demonstrated that CIHH treatment improves fracture healing, increases bone mineral density, and increases bone strength via the activation of HIF-1α and bone production-related genes.
Highlights
Bone fracture is a common clinical disease, including traumatic fracture, pathologic fracture, and periprosthetic fracture
The callus amount was significantly increased in chronic intermittent hypobaric hypoxia (CIHH) rats at week 4, and the remodeling of fracture healing was almost finished in CIHH rats
The results revealed that CIHH treatment can increase callus production and accelerate bone fracture healing
Summary
Bone fracture is a common clinical disease, including traumatic fracture, pathologic fracture, and periprosthetic fracture. There are several strategies to enhance fracture healing clinically [6]. It can be divided into the biophysical and biological strategy. The biological strategy includes autologous bone marrow, peptide signaling molecules, and morphogenetic factors treatment (bone morphogenetic proteins and Wnt proteins) [6]. Bone morphogenetic protein 2 (BMP-2) and bone morphogenetic protein 7 (BMP-7) are the only FDA-approved therapies to promote fracture healing [7]. Compared with autologous bone transplantation, treatment with BMP-7 did not significantly improve fracture healing [6]. It can cause local complications as well as serious side effects [10]. Safe and effective treatment after fracture remains to be developed
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