Preventing periprosthetic osteolysis in aging populations through lymphatic activation and stem cell-associated secretory phenotype inhibition.
Chen ZhaoKewei RongPengcheng LiuKeyu KongHaikuo LiPu ZhangXuzhuo ChenQiang FuXiaoqing WangPublished in: Communications biology (2024)
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.
Keyphrases
- lymph node
- mesenchymal stem cells
- bone loss
- endothelial cells
- replacement therapy
- stem cells
- bone mineral density
- signaling pathway
- soft tissue
- high fat diet induced
- umbilical cord
- total hip
- ejection fraction
- inflammatory response
- prognostic factors
- body composition
- total knee arthroplasty
- small molecule
- weight gain
- physical activity
- insulin resistance
- amino acid
- cell therapy