PDF(Pubmed)
Abstract：
With increases in life expectancy, the number of patients requiring joint replacement therapy and experiencing periprosthetic osteolysis, the most common complication leading to implant failure, is growing or underestimated. In this study, we found that osteolysis progression and osteoclast differentiation in the surface of the skull bone of adult mice were accompanied by significant expansion of lymphatic vessels within bones. Using recombinant VEGF-C protein to activate VEGFR3 and promote proliferation of lymphatic vessels in bone, we counteracted excessive differentiation of osteoclasts and osteolysis caused by titanium alloy particles or inflammatory cytokines LPS/TNF-α. However, this effect was not observed in aged mice because adipogenically differentiated mesenchymal stem cells (MSCs) inhibited the response of lymphatic endothelial cells to agonist proteins. The addition of the JAK inhibitor ruxolitinib restored the response of lymphatic vessels to external stimuli in aged mice to protect against osteolysis progression. These findings suggest that inhibiting SASP secretion by adipogenically differentiated MSCs while activating lymphatic vessels in bone offers a new method to prevent periprosthetic osteolysis during joint replacement follow-up.
摘要：
随着预期寿命的增加，需要关节置换治疗和假体周围骨质溶解的患者数量，导致植入物失败的最常见并发症，增长或被低估。在这项研究中,我们发现成年小鼠颅骨表面的骨溶解进展和破骨细胞分化伴随着骨内淋巴管的显著扩张。利用重组VEGF-C蛋白激活VEGFR3,促进骨淋巴管增殖,我们对抗了钛合金颗粒或炎性细胞因子LPS/TNF-α引起的破骨细胞过度分化和骨溶解。然而,在老年小鼠中未观察到这种效应,因为脂肪分化的间充质干细胞(MSCs)抑制了淋巴管内皮细胞对激动剂蛋白的反应.添加JAK抑制剂ruxolitinib可恢复老年小鼠淋巴管对外部刺激的反应，以防止骨质溶解进展。这些发现表明，抑制脂肪分化的MSCs分泌SASP，同时激活骨骼中的淋巴管，为预防关节置换随访期间假体周围骨质溶解提供了一种新方法。
