College of Basic Medicine, Shaanxi University of Chinese Medicine, Xi'an-Xianyang New Economic Zone, Xianyang, 712046, China.
Department of Biomedical Engineering, Fourth Military Medical University, 17 West Changle Road, Xi'an, 710032, China.
Osteoporos Int. 2018 May;29(5):1177-1191. doi: 10.1007/s00198-018-4392-1. Epub 2018 Mar 9.
UNLABELLED: The effects of exogenous pulsed electromagnetic field (PEMF) stimulation on T1DM-associated osteopathy were investigated in alloxan-treated rabbits. We found that PEMF improved bone architecture, mechanical properties, and porous titanium (pTi) osseointegration by promoting bone anabolism through a canonical Wnt/β-catenin signaling-associated mechanism, and revealed the clinical potential of PEMF stimulation for the treatment of T1DM-associated bone complications. INTRODUCTION: Type 1 diabetes mellitus (T1DM) is associated with deteriorated bone architecture and impaired osseous healing potential; nonetheless, effective methods for resisting T1DM-associated osteopenia/osteoporosis and promoting bone defect/fracture healing are still lacking. PEMF, as a safe and noninvasive method, have proven to be effective for promoting osteogenesis, whereas the potential effects of PEMF on T1DM osteopathy remain poorly understood. METHODS: We herein investigated the effects of PEMF stimulation on bone architecture, mechanical properties, bone turnover, and its potential molecular mechanisms in alloxan-treated diabetic rabbits. We also developed novel nontoxic Ti2448 pTi implants with closer elastic modulus with natural bone and investigated the impacts of PEMF on pTi osseointegration for T1DM bone-defect repair. RESULTS: The deteriorations of cancellous and cortical bone architecture and tissue-level mechanical strength were attenuated by 8-week PEMF stimulation. PEMF also promoted osseointegration and stimulated more adequate bone ingrowths into the pore spaces of pTi in T1DM long-bone defects. Moreover, T1DM-associated reduction of bone formation was significantly attenuated by PEMF, whereas PEMF exerted no impacts on bone resorption. We also found PEMF-induced activation of osteoblastogenesis-related Wnt/β-catenin signaling in T1DM skeletons, but PEMF did not alter osteoclastogenesis-associated RANKL/RANK signaling gene expression. CONCLUSION: We reveal that PEMF improved bone architecture, mechanical properties, and pTi osseointegration by promoting bone anabolism through a canonical Wnt/β-catenin signaling-associated mechanism. This study enriches our basic knowledge for understanding skeletal sensitivity in response to external electromagnetic signals, and also opens new treatment alternatives for T1DM-associated osteopenia/osteoporosis and osseous defects in an easy and highly efficient manner.
目的:研究外源性脉冲电磁场(PEMF)刺激对链脲佐菌素(alloxan)诱导的 1 型糖尿病(T1DM)相关骨病的影响。
方法:我们发现 PEMF 通过经典的 Wnt/β-catenin 信号通路相关机制促进骨合成代谢,改善了骨结构、力学性能和多孔钛(pTi)的骨整合,从而改善了骨结构、力学性能和多孔钛(pTi)的骨整合,揭示了 PEMF 刺激治疗 T1DM 相关骨并发症的临床潜力。
结果:8 周的 PEMF 刺激可减轻松质骨和皮质骨结构以及组织水平力学强度的恶化。PEMF 还促进了 T1DM 长骨缺损中 pTi 的骨整合,并刺激了更多的骨进入 pTi 的孔隙。此外,T1DM 相关的骨形成减少明显被 PEMF 减弱,而 PEMF 对骨吸收没有影响。我们还发现 PEMF 诱导的 T1DM 骨骼中成骨细胞相关 Wnt/β-catenin 信号的激活,但 PEMF 不改变破骨细胞相关 RANKL/RANK 信号基因表达。
结论:我们揭示了 PEMF 通过经典的 Wnt/β-catenin 信号通路相关机制促进骨合成代谢,改善了骨结构、力学性能和 pTi 的骨整合。这项研究丰富了我们对骨骼对外界电磁信号的敏感性的基本认识,为 T1DM 相关骨质疏松/骨量减少和骨缺损的治疗提供了新的选择。
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