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
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
复制标题
低 1 级机械振动通过促进 1 型糖尿病兔的合成代谢反应来改善骨微结构、组织机械性能和多孔钛种植体骨整合。
DOI：
10.1016/j.bone.2017.10.001
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发表时间：
2018-01-01
期刊：
影响因子：
4.1
通讯作者：
Luo, Erping
中科院分区：
文献类型：
--
作者：
Jing, Da;Yan, Zedong;Luo, Erping
1型糖尿病（T1 DM）与骨量减少、骨折风险增加和骨缺损再生潜力受损相关。由于T1 DM人群的迅速增加，这些骨骼并发症正在成为重要的临床挑战，这需要开发T1 DM相关骨质减少/骨质疏松症和骨创伤的有效治疗。本研究旨在探讨全身振动（whole body vibration，WBV）对四氧嘧啶糖尿病兔骨微结构、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只四氧嘧啶治疗的糖尿病兔平均分配到对照组、DM组和DM + WBV刺激（WBV）组。在所有家兔的左侧股骨外侧髁上建立圆柱形钻孔缺损，并用新型无毒Ti 2448 pTi填充。WBV组每天暴露于WBV（0.3g，30 Hz）1h，连续8周。处死后，收获左股骨髁进行组织学、组织形态计量学和纳米压痕分析。将缺损上方2 cm高的股骨样本用于qRT-PCR分析。右侧股骨远端进行mu CT扫描。我们发现，所有四氧嘧啶治疗的家兔在整个实验期间表现出高血糖。通过mu CT、组织学和纳米压痕检查，WBV抑制了松质骨和皮质骨结构以及组织水平机械性能的恶化。T1 DM诱导的骨形成减少被WBV抑制，如血清OCN升高和矿物质沉积率（MAR）增加所证明的，而骨吸收未观察到改变。标记TRACP 5 b。WBV还刺激了矿化骨组织更充分地长入pTi孔隙，并改善了T1 DM骨缺损中种植体周围骨组织水平的机械性能和MAR。WBV减轻了T1 DM兔股骨BMP 2、OCN、Wnt 3a、Lrp 6和β-连环蛋白的降低，并抑制了Sost mRNA表达，但未改变RANKL或RANK基因表达。我们的研究结果表明，WBV通过促进经典Wnt信号介导的骨骼合成代谢反应，改善骨结构，组织水平的机械性能和pTi骨整合。这项研究不仅促进了我们对T1 DM骨骼敏感性对外部机械提示的反应的理解，而且还以经济高效的方式为T1 DM相关骨质减少/骨质疏松症和骨缺损提供了新的治疗选择。(C)2017爱思唯尔公司All rights reserved.
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 1 h/day WBV (0.3 g, 30 Hz) for 8 weeks. After sacrifice, the left femoral condyles were harvested for histological, histomorphometric and nano indentation analyses. The femoral sample with 2-cm height above the defect was used for qRT-PCR analysis. The right distal femora were scanned with mu CT. 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 mu CT, 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 beta-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. (C) 2017 Elsevier Inc. All rights reserved.