Liu Yanshi, Liu Jialin, Cai Feiyu, Liu Kai, Zhang Xiaoxu, Yusufu Aihemaitijiang
Department of Trauma and Microreconstructive Surgery, The First Affiliated Hospital of Xinjiang Medical University, Ürümqi, China.
Department of Prosthodontics, The First Affiliated Hospital of Xinjiang Medical University, Ürümqi, China.
Front Physiol. 2022 Feb 22;13:804469. doi: 10.3389/fphys.2022.804469. eCollection 2022.
Hypoxia is the critical driving force for angiogenesis and can trigger the osteogenic-angiogenic coupling followed by the enhancement of bone regeneration. While lots of studies showed that hypoxia administration can accelerate bone formation during distraction osteogenesis (DO), the therapeutic timing for the osteogenic purpose was concentrated on the distraction phase. The outcomes of hypoxia administration in the consolidation phase stay uncertain. The purpose of this study was to determine the osteogenic effectiveness of hypoxia therapy during the consolidation phase, if any, to enhance bone regeneration in a rat femoral DO model.
A total of 42 adult male Sprague-Dawley rats underwent right femoral mid-diaphysis transverse osteotomy and were randomly divided into Control (NS administration, = 21) and Group1 (deferoxamine therapy, = 21) after distraction. During the consolidation phase, Group1 was treated with local deferoxamine (DFO) injection into the distraction zone, while the Control underwent the same dosage of NS. Animals were sacrificed after 2, 4, and 6 weeks of consolidation. The process of bone formation and remodeling was monitored by digital radiographs, and the regenerated bone was evaluated by micro-computed tomography (micro-CT), biomechanical test, and histological analysis. The serum content of hypoxia-inducible factor 1α (HIF-1α) and vascular endothelial growth factor (VEGF) were measured by enzyme linked immunosorbent assay (ELISA) for further analysis.
Bone regeneration was significantly enhanced after hypoxia therapy during the consolidation phase. The digital radiograph, micro-CT, and biomechanical evaluation showed better effects regarding volume, continuity, and mechanical properties of the regenerated bone in Group1. The histomorphological evaluation also revealed the hypoxia treatment contributed to accelerate bone formation and remodeling during DO. The higher positive expression of angiogenic and osteogenic markers were observed in Group1 after hypoxia administration according to the immunohistochemical analysis. The serum content of HIF-1α and VEGF was also increased after hypoxia therapy as evidenced from ELISA.
Hypoxia administration during the consolidation phase of distraction osteogenesis has benefits in enhancing bone regeneration, including accelerates the bone formation and remodeling.
缺氧是血管生成的关键驱动力，可触发成骨-血管生成耦合，进而促进骨再生。虽然许多研究表明，缺氧处理可在牵张成骨（DO）过程中加速骨形成，但成骨目的的治疗时机主要集中在牵张期。缺氧处理在巩固期的效果仍不确定。本研究的目的是确定在巩固期进行缺氧治疗对增强大鼠股骨DO模型骨再生的成骨效果（若有的话）。
42只成年雄性Sprague-Dawley大鼠接受右股骨干中段横向截骨术，牵张后随机分为对照组（给予生理盐水，n = 21）和1组（去铁胺治疗，n = 21）。在巩固期，1组在牵张区局部注射去铁胺（DFO），而对照组注射相同剂量的生理盐水。巩固2、4和6周后处死动物。通过数字X线片监测骨形成和重塑过程，并通过微型计算机断层扫描（micro-CT）、生物力学测试和组织学分析评估再生骨。通过酶联免疫吸附测定（ELISA）测量血清中缺氧诱导因子1α（HIF-1α）和血管内皮生长因子（VEGF）的含量以进行进一步分析。
巩固期进行缺氧治疗后骨再生显著增强。数字X线片、micro-CT和生物力学评估显示，1组再生骨的体积、连续性和力学性能方面效果更好。组织形态学评估还显示，缺氧处理有助于在DO过程中加速骨形成和重塑。免疫组织化学分析显示，缺氧处理后1组血管生成和成骨标志物的阳性表达更高。ELISA结果表明，缺氧治疗后血清中HIF-1α和VEGF的含量也增加。
牵张成骨巩固期进行缺氧治疗有利于增强骨再生，包括加速骨形成和重塑。
