Orthopaedic Research Laboratory, Aarhus University Hospital, 8200 Aarhus, Denmark.
Comparative Medicine Laboratory, Aarhus University, 8200 Aarhus, Denmark.
Int J Mol Sci. 2021 Dec 28;23(1):323. doi: 10.3390/ijms23010323.
Systemic Intermittent Hypoxic Therapy (IHT) relies on the adaptive response to hypoxic stress. We investigated allogenic bone-graft resorption in the lumbar spine in 48 mice. The mice were exposed to IHT for 1 week before surgery or 1 week after surgery and compared with controls after 1 and 4 weeks. Complete graft resorption was observed in 33-36% of the animals in the control group, but none in the preoperative IHT group. Increased bone-graft volume was demonstrated by micro-computed tomography in the preoperative IHT group after 1 week ( = 0.03) while a non-significant difference was observed after 4 weeks ( = 0.12). There were no significant differences in the postoperative IHT group. Increased concentration of immune cells was localized in the graft area, and more positive tartrate-resistant acid phosphatase (TRAP) staining was found in controls compared with IHT allogenic bone grafts. Systemic IHT resulted in a significant increase of the major osteoclast inhibitor osteoprotegerin as well as osteogenic and angiogenic regulators Tgfbr3, Fst3l, Wisp1, and Vegfd. Inflammatory cytokines and receptor activator of nuclear factor kappa-B ligand (RANKL) stimulators IL-6, IL-17a, IL-17f, and IL-23r increased after 1 and 4 weeks, and serum RANKL expression remained constant while Ccl3 and Ccl5 decreased. We conclude that the adaptive response to IHT activates numerous pathways leading to inhibition of osteoclastic activity and inhibition of allogenic bone-graft resorption.
系统性间歇性低氧治疗（IHT）依赖于对低氧应激的适应性反应。我们在 48 只小鼠中研究了腰椎异体骨移植物的吸收。在手术前 1 周或手术后 1 周，将小鼠暴露于 IHT 中，并在 1 周和 4 周后与对照组进行比较。在对照组中，有 33-36%的动物完全吸收了移植物，但在术前 IHT 组中没有。在术前 IHT 组中，在 1 周时通过微计算机断层扫描（micro-CT）显示出增加的骨移植物体积（=0.03），而在 4 周时观察到非显著性差异（=0.12）。在术后 IHT 组中没有显著差异。免疫细胞的浓度增加定位在移植物区域，与 IHT 异体骨移植物相比，对照组中发现更多的抗酒石酸酸性磷酸酶（TRAP）染色阳性。全身 IHT 导致主要破骨细胞抑制剂骨保护素（osteoprotegerin）以及成骨和血管生成调节剂 TGFBR3、FST3L、WISP1 和 VEGFD 的浓度显著增加。在 1 周和 4 周后，炎症细胞因子和核因子 kappa-B 配体受体激活剂（receptor activator of nuclear factor kappa-B ligand，RANKL）刺激物 IL-6、IL-17a、IL-17f 和 IL-23r 增加，而血清 RANKL 表达保持不变，而 CCL3 和 CCL5 减少。我们得出结论，对 IHT 的适应性反应激活了许多途径，导致抑制破骨细胞活性和抑制异体骨移植物吸收。
