Pulsed electromagnetic fields modify the adverse effects of glucocorticoids on bone architecture, bone strength and porous implant osseointegration by rescuing bone-anabolic actions
Pulsed electromagnetic fields modify the adverse effects of glucocorticoids on bone architecture, bone strength and porous implant osseointegration by rescuing bone-anabolic actions
复制标题
脉冲电磁场通过挽救骨合成代谢作用来改变糖皮质激素对骨结构、骨强度和多孔植入物骨整合的不利影响
DOI：
10.1016/j.bone.2020.115266
复制
发表时间：
2020-04-01
期刊：
影响因子：
4.1
通讯作者：
Jing, Da
中科院分区：
文献类型：
--
作者：
Cai, Jing;Shao, Xi;Jing, Da
已知长期糖皮质激素治疗可诱导骨脆性增加和骨骼再生潜力受损。越来越多的证据表明，脉冲电磁场（PEMF）可以加速骨折愈合，增加骨量的实验和临床。然而，糖皮质激素处理的骨和骨细胞如何响应PEMF刺激仍然知之甚少。在这里，我们测试了PEMF对地塞米松治疗（0.5 mg/kg/天，6周）的家兔的骨量/质量、骨代谢和多孔种植体骨整合的影响。显微CT、组织学和纳米压痕结果表明，PEMF改善了糖皮质激素介导的松质骨和皮质骨结构和内在材料性能的恶化。利用低毒性和低弹性模量的新型多孔钛种植体（Ti 2448），我们发现，在糖皮质激素治疗的兔骨缺损修复过程中，PEMF刺激骨长入种植体孔隙，并提高笔式种植体骨材料质量。动态组织形态计量学结果显示，PEMF逆转了糖皮质激素对骨形成的不利影响，这是通过增加循环骨钙素和P1 NP证实的。PEMF还显著减弱骨细胞凋亡，促进成骨细胞相关的骨钙素，Runx 2和Osx的表达，并抑制骨细胞特异性DKK 1和Sost表达（成骨细胞的负调节因子）在糖皮质激素处理的骨骼，揭示改善成骨细胞和骨细胞的功能活动。然而，PEMF对循环骨吸收细胞因子（血清TRAcP 5 b和CTX-1）或破骨细胞特异性标志物（TRAP和组织蛋白酶K）的骨骼基因表达没有影响。PEMF还显著上调了典型Wnt配体（Wnt 1，Wnt 3a和Wnt 10 b）的骨骼基因表达，而PENT没有改变非典型Wnt 5a的表达。这项研究表明，PEMF治疗通过促进有效的骨合成代谢作用，改善糖皮质激素治疗兔的骨量，强度和多孔种植体骨整合，这与成骨细胞和骨细胞功能的典型Wnt介导的改善有关。本研究为糖皮质激素相关性骨病提供了一种简便、无创的治疗方法。
Long-term glucocorticoid therapy is known to induce increased bone fragility and impaired skeletal regeneration potential. Growing evidence suggests that pulsed electromagnetic fields (PEMF) can accelerate fracture healing and increase bone mass both experimentally and clinically. However, how glucocorticoid-treated bone and bone cells respond to PEMF stimulation remains poorly understood. Here we tested the effects of PEMF on bone quantity/quality, bone metabolism, and porous implant osseointegration in rabbits treated with dexamethasone (0.5 mg/kg/day, 6 weeks). The micro-CT, histologic and nanoindentation results showed that PEMF ameliorated the glucocorticoid-mediated deterioration of cancellous and cortical bone architecture and intrinsic material properties. Utilizing the new porous titanium implant (Ti2448) with low toxicity and low elastic modulus, we found that PEMF stimulated bone ingrowth into the pores of implants and enhanced pen-implant bone material quality during osseous defect repair in glucocorticoid-treated rabbits. Dynamic histomorphometric results revealed that PEMF reversed the adverse effects of glucocorticoids on bone formation, which was confirmed by increased circulating osteocalcin and P1NP. PEMF also significantly attenuated osteocyte apoptosis, promoted osteoblast-related osteocalcin, Runx2 and Osx expression, and inhibited osteocyte-specific DKK1 and Sost expression (negative regulators of osteoblasts) in glucocorticoid-treated skeletons, revealing improved functional activities of osteoblasts and osteocytes. Nevertheless, PEMF exerted no effect on circulating bone-resorbing cytokines (serum TRAcP5b and CTX-1) or skeletal gene expression of osteoclast-specific markers (TRAP and cathepsin K). PEMF also significantly upregulated skeletal gene expression of canonical Wnt ligands (Wnt1, Wnt3a and Wnt10b), whereas PENT did not alter non-canonical Wnt5a expression. This study demonstrates that PEMF treatment improves bone mass, strength and porous implant osseointegration in glucocorticoid-treated rabbits by promoting potent bone-anabolic action, which is associated with canonical Wnt-mediated improvement in osteoblast and osteocyte functions. This study provides a new treatment alternative for glucocorticoid-related bone disorders in a convenient and non-invasive manner.