Turner Russell T, Philbrick Kenneth A, Wong Carmen P, Fichter Aidan R, Branscum Adam J, Iwaniec Urszula T
J Endocrinol. 2025 Feb 17;264(3). doi: 10.1530/JOE-24-0324. Print 2025 Mar 1.
Leptin increases focal inflammation and osteolysis induced by polyethylene particles in leptin-deficient ob/ob mice, suggesting that this adipokine, an important immune modulator, contributes to orthopedic implant failure. Focal inflammation leads to bone loss at distant skeletal sites, and it is plausible that leptin also contributes to this response. We tested this possibility in 6-week-old female ob/ob mice (6-8/group) by evaluating bone architecture, turnover and gene expression 12 days following the surgical placement of polyethylene particles over the calvaria. Particle treatment had minimal effect on bone mass, density or cancellous bone architecture in the femur and 5th lumbar vertebra (LV). However, compared to controls, particle treatment altered tibial expression levels of 32/84 genes related to bone metabolism. Subcutaneous infusion of leptin (6 μg/d) to mice following the placement of polyethylene particles over the calvaria (combination treatment) resulted in cancellous bone loss in the distal femur metaphysis and LV and in the differential expression of 34/84 genes, 15 of which overlapped with particle treatment. Notably, combination treatment, but not particle treatment, resulted in increased expression of genes strongly associated with bone turnover and response to inflammation. Leptin treatment alone (0.1-10 μg/day) did not result in bone loss in the femur or LV in the ob/ob mice. These findings suggest that leptin exaggerates the detrimental effects of particle-induced inflammation on bone turnover balance, leading to systemic bone loss.
瘦素会加剧瘦素缺乏的ob/ob小鼠中由聚乙烯颗粒诱导的局部炎症和骨溶解，这表明这种作为重要免疫调节因子的脂肪因子会导致骨科植入物失败。局部炎症会导致远处骨骼部位的骨质流失，瘦素也可能促成了这种反应。我们通过评估在颅骨上手术植入聚乙烯颗粒12天后的骨结构、骨转换和基因表达，在6周龄雌性ob/ob小鼠（每组6 - 8只）中测试了这种可能性。颗粒处理对股骨和第五腰椎（LV）的骨量、骨密度或松质骨结构影响极小。然而，与对照组相比，颗粒处理改变了与骨代谢相关的84个基因中的32个在胫骨中的表达水平。在颅骨上放置聚乙烯颗粒后对小鼠皮下输注瘦素（6μg/天）（联合处理）导致股骨远端干骺端和LV的松质骨流失以及84个基因中的34个基因的差异表达，其中15个与颗粒处理的基因重叠。值得注意的是，联合处理而非颗粒处理导致与骨转换和炎症反应密切相关的基因表达增加。单独给予瘦素处理（0.1 - 10μg/天）并未导致ob/ob小鼠的股骨或LV骨质流失。这些发现表明，瘦素会夸大颗粒诱导的炎症对骨转换平衡的有害影响，导致全身性骨质流失。
