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低水平机械振动通过促进 1 型糖尿病兔的合成代谢反应,改善骨微结构、组织力学性能和多孔钛植入物的骨整合。

Low-1 level mechanical vibration improves bone microstructure, tissue mechanical properties and porous titanium implant osseointegration by promoting anabolic response in type 1 diabetic rabbits.

机构信息

Department of Biomedical Engineering, Fourth Military Medical University, Xi'an, China; Department of Orthopedics, Xijing Hospital, Fourth Military Medical University, Xi'an, China.

Department of Biomedical Engineering, Fourth Military Medical University, Xi'an, China.

出版信息

Bone. 2018 Jan;106:11-21. doi: 10.1016/j.bone.2017.10.001. Epub 2017 Oct 2.


DOI:10.1016/j.bone.2017.10.001
PMID:28982588
Abstract

Type 1 diabetes mellitus (T1DM) is associated with reduced bone mass, increased fracture risk, and impaired bone defect regeneration potential. These skeletal complications are becoming important clinical challenges due to the rapidly increasing T1DM population, which necessitates developing effective treatment for T1DM-associated osteopenia/osteoporosis and bone trauma. This study aims to investigate the effects of whole-body vibration (WBV), an easy and non-invasive biophysical method, on bone microstructure, tissue-level mechanical properties and porous titanium (pTi) osseointegration in alloxan-diabetic rabbits. Six non-diabetic and twelve alloxan-treated diabetic rabbits were equally assigned to the Control, DM, and DM with WBV stimulation (WBV) groups. A cylindrical drill-hole defect was established on the left femoral lateral condyle of all rabbits and filled with a novel non-toxic Ti2448 pTi. Rabbits in the WBV group were exposed to 1h/day WBV (0.3g, 30Hz) for 8weeks. After sacrifice, the left femoral condyles were harvested for histological, histomorphometric and nanoindentation analyses. The femoral sample with 2-cm height above the defect was used for qRT-PCR analysis. The right distal femora were scanned with μCT. We found that all alloxan-treated rabbits exhibited hyperglycemia throughout the experimental period. WBV inhibited the deterioration of cancellous and cortical bone architecture and tissue-level mechanical properties via μCT, histological and nanoindentation examinations. T1DM-induced reduction of bone formation was inhibited by WBV, as evidenced by elevated serum OCN and increased mineral apposition rate (MAR), whereas no alteration was observed in bone resorption marker TRACP5b. WBV also stimulated more adequate ingrowths of mineralized bone tissue into pTi pore spaces, and improved peri-implant bone tissue-level mechanical properties and MAR in T1DM bone defects. WBV mitigated the reductions in femoral BMP2, OCN, Wnt3a, Lrp6, and β-catenin and inhibited Sost mRNA expression but did not alter RANKL or RANK gene expression in T1DM rabbits. Our findings demonstrated that WBV improved bone architecture, tissue-level mechanical properties, and pTi osseointegration by promoting canonical Wnt signaling-mediated skeletal anabolic response. This study not only advances our understanding of T1DM skeletal sensitivity in response to external mechanical cues but also offers new treatment alternatives for T1DM-associated osteopenia/osteoporosis and osseous defects in an economic and highly efficient manner.

摘要

1 型糖尿病(T1DM)与骨量减少、骨折风险增加和骨缺损再生潜力受损有关。由于 T1DM 患者人数迅速增加,这些骨骼并发症成为重要的临床挑战,因此需要开发有效的治疗方法来治疗 T1DM 相关的骨质疏松症/骨量减少和骨创伤。本研究旨在探讨全身振动(WBV)作为一种简单、非侵入性的生物物理方法,对丙烯醛糖尿病兔骨微结构、组织水平力学性能和多孔钛(pTi)骨整合的影响。将 6 只非糖尿病兔和 12 只丙烯醛处理的糖尿病兔平均分配到对照组、DM 组和 DM 加 WBV 刺激(WBV)组。所有兔子的左侧股骨外侧髁上建立圆柱形钻孔缺陷,并填充新型无毒 Ti2448 pTi。WBV 组的兔子每天暴露于 1h WBV(0.3g,30Hz)8 周。处死前,取左侧股骨髁进行组织学、组织形态计量学和纳米压痕分析。使用缺陷上方 2cm 高度的股骨样本进行 qRT-PCR 分析。右侧远端股骨用 μCT 扫描。我们发现所有丙烯醛处理的兔子在整个实验期间都表现出高血糖。通过 μCT、组织学和纳米压痕检查,WBV 抑制了松质骨和皮质骨结构和组织水平力学性能的恶化。WBV 抑制了 T1DM 诱导的骨形成减少,这表现在血清 OCN 升高和矿化沉积率(MAR)增加,而骨吸收标志物 TRACP5b 没有变化。WBV 还刺激了更多矿化骨组织进入 pTi 孔隙,改善了 T1DM 骨缺损中植入物周围骨组织水平的力学性能和 MAR。WBV 减轻了 T1DM 兔股骨中 BMP2、OCN、Wnt3a、Lrp6 和β-catenin 的减少,并抑制了 Sost mRNA 的表达,但没有改变 RANKL 或 RANK 基因的表达。我们的研究结果表明,WBV 通过促进经典 Wnt 信号转导介导的骨骼合成代谢反应,改善了骨结构、组织水平力学性能和 pTi 骨整合。这项研究不仅提高了我们对 T1DM 骨骼对外界机械刺激的敏感性的理解,还为 T1DM 相关骨质疏松症/骨量减少和骨缺损提供了新的治疗选择,具有经济高效的特点。

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[3]
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[4]
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[5]
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[6]
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