PDF(Pubmed)
Abstract：
Spinal pain affects individuals of all ages and is the most common musculoskeletal problem globally. Its clinical management remains a challenge as the underlying mechanisms leading to it are still unclear. Here, we report that significantly increased numbers of senescent osteoclasts (SnOCs) are observed in mouse models of spinal hypersensitivity, like lumbar spine instability (LSI) or aging, compared to controls. The larger population of SnOCs is associated with induced sensory nerve innervation, as well as the growth of H-type vessels, in the porous endplate. We show that deletion of senescent cells by administration of the senolytic drug Navitoclax (ABT263) results in significantly less spinal hypersensitivity, spinal degeneration, porosity of the endplate, sensory nerve innervation, and H-type vessel growth in the endplate. We also show that there is significantly increased SnOC-mediated secretion of Netrin-1 and NGF, two well-established sensory nerve growth factors, compared to non-senescent OCs. These findings suggest that pharmacological elimination of SnOCs may be a potent therapy to treat spinal pain.
摘要：
脊柱疼痛影响所有年龄段的人，是全球最常见的肌肉骨骼问题。其临床管理仍然是一个挑战，因为导致其的潜在机制仍不清楚。这里,我们报道，在脊髓超敏反应的小鼠模型中观察到衰老的破骨细胞（SnOCs）数量显着增加，如腰椎不稳定（LSI）或老化，与对照组相比。大量SnOCs与诱导的感觉神经支配有关，以及H型血管的生长，在多孔端板中。我们表明，通过施用抗衰老药物Navitoclax（ABT263）删除衰老细胞导致脊髓超敏反应明显减少，脊髓变性,端板的孔隙度，感觉神经支配,和端板中H型血管生长。我们还显示SnOC介导的Netrin-1和NGF的分泌显着增加，两种公认的感觉神经生长因子，与非衰老OCs相比。这些发现表明，药物消除SnOCs可能是治疗脊柱疼痛的有效疗法。
