Effects of remote ischemic post‑conditioning on fracture healing in rats.
Remote ischemic post‑conditioning (RIPC) is an established method to activate the hypoxia‑inducible factor‑1α (HIF‑1α) pathway, which is involved in the impairment of fracture healing. However, the role of RIPC in fracture healing remains to be fully elucidated. In the present study, rats received fractures and were divided into two groups: Control and RIPC, in which hind limb occlusion was performed. Rats were sacrificed at 7, 14, 28 and 42 days subsequent to tibial fracture. Micro‑computed tomography was performed to measure healing of the bone tissue and biomechanical testing was used to test mechanical strength. In addition, the effects of hind limb occlusion on the expression of two primary angiogenic mediators, HIF‑1α and vascular endothelial growth factor (VEGF), as well as the osteoblast markers runt‑related transcription factor 2 (Runx2), alkaline phosphatase (ALP) and osteocalcin (OCN), were determined at the mRNA and protein levels by reverse transcription‑quantitative polymerase chain reaction, western blot analysis and immunohistochemistry. Systemic administration of hind limb occlusion (3 cycles/day, with each occlusion or release phase lasting 10 min) significantly promoted fracture healing and mechanical strength. The present study demonstrated that in rats treated with hind limb occlusion, the expression of HIF‑1α, VEGF, Runx2, ALP and OCN was significantly increased at the mRNA and protein levels, and that RIPC enhances fracture repair in vivo.
Department of Orthopedics, Xuanwu Hospital, Capital Medical University, Beijing 100053, P.R. China.
Meng
M
Zhou
Department of Orthopedics, Xuanwu Hospital, Capital Medical University, Beijing 100053, P.R. China.
Shibao
S
Lu
Institute of Hypoxia Medicine, Xuanwu Hospital, Capital Medical University, Beijing 100053, P.R. China.
Guowei
G
Lu
Department of Orthopedics, Xuanwu Hospital, Capital Medical University, Beijing 100053, P.R. China.
Jiang
J
Huang
Department of Orthopedics, Xuanwu Hospital, Capital Medical University, Beijing 100053, P.R. China.
Limin
L
Liu
Department of Orthopedics, Xuanwu Hospital, Capital Medical University, Beijing 100053, P.R. China.
Shuai
S
An
Department of Orthopedics, Xuanwu Hospital, Capital Medical University, Beijing 100053, P.R. China.
Zheng
Z
Li
Department of Orthopedics, Xuanwu Hospital, Capital Medical University, Beijing 100053, P.R. China.
Huiliang
H
Shen
D000469:Alkaline Phosphatase / Q000235:genetics / Q000378:metabolism; D000818:Animals; D050659:Core Binding Factor Alpha 1 Subunit / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D017102:Fracture Healing; D050723:Fractures, Bone / Q000378:metabolism / Q000473:pathology*; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics / Q000378:metabolism; D057775:Ischemic Postconditioning; D008297:Male; D015675:Osteocalcin / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013977:Tibia / Q000098:blood supply* / Q000000981:diagnostic imaging / Q000503:physiopathology; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism; D055114:X-Ray Microtomography
D050659:Core Binding Factor Alpha 1 Subunit; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; D015675:Osteocalcin; D000469:Alkaline Phosphatase