College of Basic Medicine, Shaanxi University of Chinese Medicine, Xianyang, China; Department of Biomedical Engineering, Fourth Military Medical University, Xi'an, China.
Department of Biomedical Engineering, Fourth Military Medical University, Xi'an, China.
Bone. 2020 Apr;133:115266. doi: 10.1016/j.bone.2020.115266. Epub 2020 Feb 7.
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 peri-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 PEMF 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.
长期使用糖皮质激素会导致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）可以在实验和临床中加速骨折愈合和增加骨量。然而，糖皮质激素处理的骨骼和骨细胞对 PEMF 刺激的反应仍知之甚少。在这里，我们测试了 PEMF 对接受地塞米松（0.5mg/kg/天，6 周）治疗的兔子的骨量/质量、骨代谢和多孔植入物骨整合的影响。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特性的恶化。利用具有低毒性和低弹性模量的新型多孔钛植入物（Ti2448），我们发现 PEMF 刺激了骨细胞向植入物孔内生长，并在糖皮质激素治疗的兔子骨缺损修复过程中增强了植入物周围骨材料的质量。动态组织形态计量学结果表明，PEMF 逆转了糖皮质激素对骨形成的不利影响，这通过增加循环骨钙素和 P1NP 得到证实。PEMF 还显著减少了破骨细胞凋亡，促进了与成骨细胞相关的骨钙素、Runx2 和 Osx 表达，并抑制了成骨细胞特异性 DKK1 和 Sost 表达（成骨细胞的负调节剂），从而提高了成骨细胞和破骨细胞的功能活性。然而，PEMF 对循环骨吸收细胞因子（血清 TRAcP5b 和 CTX-1）或破骨细胞特异性标记物（TRAP 和组织蛋白酶 K）的骨骼基因表达没有影响。PEMF 还显著上调了骨骼中经典 Wnt 配体（Wnt1、Wnt3a 和 Wnt10b）的基因表达，而 PEMF 并未改变非经典 Wnt5a 的表达。这项研究表明，PEMF 治疗通过促进有效的骨合成作用改善了糖皮质激素治疗的兔子的骨量、强度和多孔植入物骨整合，这与经典 Wnt 介导的成骨细胞和破骨细胞功能改善有关。这项研究为糖皮质激素相关骨骼疾病提供了一种新的治疗选择，方法方便且无创。
