Center for Musculoskeletal Research, University of Rochester Medical Center, Rochester, NY, United States of America.
PLoS One. 2020 Nov 9;15(11):e0241998. doi: 10.1371/journal.pone.0241998. eCollection 2020.
Spinal fusion is a commonly performed orthopedic surgery. Autologous bone graft obtained from the iliac crest is frequently employed to perform spinal fusion. Osteogenic bone marrow stromal (a.k.a. mesenchymal stem) cells (BMSCs) are believed to be responsible for new bone formation and development of the bridging bone during spinal fusion, as these cells are located in both the graft and at the site of fusion. Our previous work revealed the importance of mitochondrial oxidative metabolism in osteogenic differentiation of BMSCs. Our objective here was to determine the impact of BMSC oxidative metabolism on osseointegration of the graft during spinal fusion. The first part of the study was focused on correlating oxidative metabolism in bone graft BMSCs to radiographic outcomes of spinal fusion in human patients. The second part of the study was focused on mechanistically proving the role of BMSC oxidative metabolism in osseointegration during spinal fusion using a genetic mouse model. Patients' iliac crest-derived graft BMSCs were identified by surface markers. Mitochondrial oxidative function was detected in BMSCs with the potentiometric probe, CMXRos. Spinal fusion radiographic outcomes, determined by the Lenke grade, were correlated to CMXRos signal in BMSCs. A genetic model of high oxidative metabolism, cyclophilin D knockout (CypD KO), was used to perform spinal fusion in mice. Graft osseointegration in mice was assessed with micro-computed tomography. Our study revealed that higher CMXRos signal in patients' BMSCs correlated with a higher Lenke grade. Mice with higher oxidative metabolism (CypD KO) had greater mineralization of the spinal fusion bridge, as compared to the control mice. We therefore conclude that higher oxidative metabolism in BMSCs correlates with better spinal fusion outcomes in both human patients and in a mouse model. Altogether, our study suggests that promoting oxidative metabolism in osteogenic cells could improve spinal fusion outcomes for patients.
脊柱融合是一种常见的矫形外科手术。自体骨取自髂嵴，常用于脊柱融合。成骨骨髓基质（也称为间充质干细胞）（BMSCs）被认为是负责脊柱融合过程中新生骨形成和桥接骨发育的细胞，因为这些细胞存在于移植物和融合部位。我们之前的工作揭示了线粒体氧化代谢在 BMSCs 成骨分化中的重要性。我们的目的是确定 BMSC 氧化代谢对脊柱融合过程中移植物骨整合的影响。研究的第一部分侧重于将骨移植物 BMSCs 的氧化代谢与人类患者脊柱融合的放射学结果相关联。研究的第二部分侧重于使用基因敲除小鼠模型从机制上证明 BMSC 氧化代谢在脊柱融合过程中骨整合中的作用。患者髂嵴来源的移植物 BMSCs 通过表面标志物鉴定。用电化学探针 CMXRos 检测 BMSCs 中的线粒体氧化功能。通过 Lenke 分级确定脊柱融合的放射学结果，并与 BMSCs 中的 CMXRos 信号相关联。使用高氧化代谢的基因模型，即亲环素 D 敲除（CypD KO），在小鼠中进行脊柱融合。用微计算机断层扫描评估小鼠移植物的骨整合情况。我们的研究表明，患者 BMSCs 中较高的 CMXRos 信号与较高的 Lenke 分级相关。与对照小鼠相比，具有较高氧化代谢（CypD KO）的小鼠的脊柱融合桥的矿化程度更大。因此，我们得出结论，BMSCs 中较高的氧化代谢与人类患者和小鼠模型中更好的脊柱融合结果相关。总的来说，我们的研究表明，促进成骨细胞中的氧化代谢可能会改善患者的脊柱融合结果。
