Guangdong Key Laboratory for Research and Development of Natural Drugs, Guangdong Medical University, Zhanjiang, People's Republic of China,
Department of Pharmaceutical Sciences, College of Pharmacy, University of Nebraska Medical Center, Omaha, NE, USA,
Clin Interv Aging. 2018 Aug 24;13:1465-1474. doi: 10.2147/CIA.S167431. eCollection 2018.
The objective of the study was to investigate the effects of glucocorticoid (GC) on the fracture healing process in a closed femur fracture mice model.
Forty 12-week-old female CD-1 mice were randomly allocated into four groups: healthy control and mice with prednisone exposure (oral gavage), 6 mg/kg/day (GC-L), 9 mg/kg/day (GC-M) and 12 mg/kg/day (GC-H). Three weeks after the initiation of prednisone dosing, closed femur fractures were created on prednisone-exposed mice and the healthy control. Prednisone administration was continued for 9 weeks post-fracture, and X-ray imaging was performed weekly to monitor the fracture healing process until the mice were euthanized. Necropsy was performed after 9 weeks and the fractured femurs were isolated and processed at necropsy for micro-CT and biomechanical property analysis. Another 20 mice (control and GC-H, 10 mice/group) were used for histology and micro-CT analysis at early time point (2-week post fracture) with continued prednisone exposure.
The results showed that oral administration of prednisone for 3 months in this strain of mice could inhibit endochondral ossification and delay the healing process, especially hard callus formation (woven bone) and bone remodeling during healing. It also could significantly decrease bone biomechanical properties.
Long-term GC administration leads to significantly delayed fracture healing and impaired bone biomechanical properties. This mouse model may be used to systematically study the cellular and molecular mechanisms underlying fracture healing with GC treatment background and may also be used to study the influence of different therapeutic interventions for bone fracture healing.
本研究旨在探讨糖皮质激素（GC）对闭合性股骨骨折小鼠模型骨折愈合过程的影响。
40 只 12 周龄雌性 CD-1 小鼠随机分为四组：健康对照组和泼尼松暴露组（灌胃），剂量分别为 6mg/kg/天（GC-L）、9mg/kg/天（GC-M）和 12mg/kg/天（GC-H）。在开始给予泼尼松 3 周后，对泼尼松暴露组和健康对照组小鼠造成闭合性股骨骨折。骨折后继续给予泼尼松治疗 9 周，每周进行 X 线成像以监测骨折愈合过程，直至处死小鼠。9 周后进行尸检，分离并处理骨折股骨进行 micro-CT 和生物力学性能分析。另外 20 只小鼠（对照组和 GC-H 组，每组 10 只）继续给予泼尼松暴露，用于早期（骨折后 2 周）的组织学和 micro-CT 分析。
结果表明，在这种小鼠品系中，连续 3 个月口服泼尼松可抑制软骨内骨化并延迟愈合过程，尤其是硬骨痂形成（编织骨）和愈合过程中的骨重塑。它还可以显著降低骨生物力学性能。
长期 GC 给药导致骨折愈合明显延迟和骨生物力学性能受损。这种小鼠模型可用于系统研究 GC 治疗背景下骨折愈合的细胞和分子机制，也可用于研究不同治疗干预措施对骨折愈合的影响。
