Wnt/β-连环蛋白激活和甲状旁腺激素激活对成年和老年雄性小鼠干骺端骨折愈合的不同影响。
Different effects of Wnt/β-catenin activation and PTH activation in adult and aged male mice metaphyseal fracture healing.
作者信息
Liu Daocheng, Qin Hao, Yang Jiazhi, Yang Lei, He Sihao, Chen Sixu, Bao Quanwei, Zhao Yufeng, Zong Zhaowen
机构信息
State Key Laboratory of Trauma, Burn and Combined Injury, Department of War Wound Rescue Skills Training, Base of Army Health Service Training, Army Medical University, Chongqing, 400042, China.
出版信息
BMC Musculoskelet Disord. 2020 Feb 19;21(1):110. doi: 10.1186/s12891-020-3138-3.
BACKGROUND
Fractures in older men are not uncommon and need to be healed as soon as possible to avoid related complications. Anti-osteoporotic drugs targeting Wnt/β-catenin and PTH (parathyroid hormone) to promote fracture healing have become an important direction in recent years. The study is to observe whether there is a difference in adult and aged situations by activating two signal paths.
METHODS
A single cortical hole with a diameter of 0.6 mm was made in the femoral metaphysis of Catnb mice and wild-type mice. The fracture healing effects of CA (Wnt/β-catenin activation) and PTH (activated by PTH (1-34) injections) were assessed by X-ray and CT imaging on days 7, 14, and 21 after fracture. The mRNA levels of β-catenin, PTH1R(Parathyroid hormone 1 receptor), and RUNX2(Runt-related transcription factor 2) in the fracture defect area were detected using RT-PCR. Angiogenesis and osteoblasts were observed by immunohistochemistry and osteoclasts were observed by TRAP (Tartrate-resistant Acid Phosphatase).
RESULT
Adult CA mice and adult PTH mice showed slightly better fracture healing than adult wild-type (WT) mice, but there was no statistical difference. Aged CA mice showed better promotion of angiogenesis and osteoblasts and better fracture healing than aged PTH mice.
CONCLUSION
The application of Wnt/β-catenin signaling pathway drugs for fracture healing in elderly patients may bring better early effects than PTH signaling pathway drugs, but the long-term effects need to be observed.
背景
老年男性骨折并不罕见，需要尽快愈合以避免相关并发症。近年来，靶向Wnt/β-连环蛋白和甲状旁腺激素（PTH）以促进骨折愈合的抗骨质疏松药物已成为一个重要方向。本研究旨在观察激活这两条信号通路在成年和老年情况下是否存在差异。
方法
在Catnb小鼠和野生型小鼠的股骨干骺端制作一个直径为0.6毫米的单皮质骨孔。在骨折后第7天、14天和21天，通过X射线和CT成像评估CA（Wnt/β-连环蛋白激活）和PTH（通过注射PTH（1-34）激活）的骨折愈合效果。使用RT-PCR检测骨折缺损区域中β-连环蛋白、PTH1R（甲状旁腺激素1受体）和RUNX2（Runx相关转录因子2）的mRNA水平。通过免疫组织化学观察血管生成和成骨细胞，通过抗酒石酸酸性磷酸酶（TRAP）观察破骨细胞。
结果
成年CA小鼠和成年PTH小鼠的骨折愈合情况略优于成年野生型（WT）小鼠，但无统计学差异。老年CA小鼠在促进血管生成和成骨细胞方面表现更好，骨折愈合情况也优于老年PTH小鼠。
结论
在老年患者中应用Wnt/β-连环蛋白信号通路药物促进骨折愈合可能比PTH信号通路药物带来更好的早期效果，但长期效果有待观察。
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