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Wnt/β-连环蛋白激活和甲状旁腺激素对小鼠股骨愈合早期骨干和干骺端的不同影响。

Different effects of Wnt/β-catenin activation and parathyroid hormone on diaphyseal and metaphyseal in the early phase of femur bone healing of mice.

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, China.

出版信息

Clin Exp Pharmacol Physiol. 2019 Jul;46(7):652-663. doi: 10.1111/1440-1681.13088. Epub 2019 Apr 21.

Abstract

Parathyroid hormone (PTH) and agents related to the manipulation of Wnt/β-catenin signalling are two promising anabolic anti-osteoporotic therapies that have been shown to promote the healing of bone fractures. Now, it is widely accepted that cortical bone and trabecular bone are two different compartments, and should be treated as separate compartments in pathological processes, such as fracture healing. It is currently unknown whether PTH and the activation of β-catenin signalling would demonstrate different effects on cortical bone and trabecular bone healing. In the current study, single 0.6-mm cortex holes were made in the femur metaphysis and diaphysis of mice, and then, PTH application and β-catenin activation were used to observe the promoting effect on bone healing. The effects of β-catenin and PTH signalling on fracture healing were observed by X-ray and CT at 3, 6, and 14 days after fracture, and the levels of β-catenin were detected by RT-PCR assay, and the number of specific antigen-positive cells of BRDU, OCN, RUNX2 was counted by immunohistochemical staining. While β-catenin activation and PTH were found to demonstrate similar effects on accelerating metaphyseal bone healing, activation of β-catenin showed a more striking effect than PTH on promoting diaphyseal bone healing. These findings might be helpful for selecting proper medication to accelerate fracture healing of different bone compartments.

摘要

甲状旁腺激素(PTH)和与 Wnt/β-连环蛋白信号通路调控相关的药物是两种有前途的促合成代谢抗骨质疏松治疗方法,已被证明可促进骨折愈合。现在,人们普遍认为皮质骨和松质骨是两个不同的部位,在骨折愈合等病理过程中应作为两个独立的部位进行治疗。目前尚不清楚 PTH 和 β-连环蛋白信号通路的激活是否会对皮质骨和松质骨的愈合产生不同的影响。在本研究中,在小鼠股骨干骺端和骨干上制造了单个 0.6-mm 皮质骨孔,然后应用 PTH 和激活β-连环蛋白信号通路来观察对骨愈合的促进作用。通过 X 射线和 CT 观察骨折后 3、6 和 14 天β-连环蛋白和 PTH 信号通路对骨折愈合的影响,并通过 RT-PCR 检测β-连环蛋白的水平,通过免疫组织化学染色计数 BRDU、OCN、RUNX2 特异性抗原阳性细胞的数量。虽然发现β-连环蛋白的激活和 PTH 对加速骺骨愈合具有相似的作用,但激活β-连环蛋白在促进骨干愈合方面的作用比 PTH 更为显著。这些发现可能有助于选择适当的药物来加速不同骨部位的骨折愈合。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cebc/6593981/d84e2904a672/CEP-46-652-g001.jpg

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