Mesenchymal stromal cells donate mitochondria to articular chondrocytes exposed to mitochondrial, environmental, and mechanical stress.
Mesenchymal stromal cells donate mitochondria to articular chondrocytes exposed to mitochondrial, environmental, and mechanical stress.
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DOI：
10.1038/s41598-022-25844-5
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发表时间：
2022-12-13
影响因子：
4.6
通讯作者：
Delco, Michelle
中科院分区：
文献类型：
--
作者：
Fahey, Megan;Bennett, Maureen;Thomas, Matthew;Montney, Kaylee;Vivancos-Koopman, Irene;Pugliese, Brenna;Browning, Lindsay;Bonassar, Lawrence J.;Delco, Michelle
关节软骨具有有限的愈合能力，并且没有药物可以预防或减缓关节损伤后骨关节炎（OA）的发展。基于间充质基质细胞（MSC）的OA再生疗法越来越常见，但有关其作用机制的问题仍然存在。我们的小组最近报道，虽然软骨是无血管的，相对代谢静止，损伤诱导软骨细胞线粒体功能障碍，驱动软骨退化和OA。已知MSC通过在高代谢组织中捐赠健康线粒体来拯救受损细胞并改善愈合，但尚未在软骨中研究线粒体转移。在这里，我们证明了骨髓间充质干细胞转移线粒体的细胞培养和损伤的软骨组织中的应力软骨细胞。已知诱导软骨细胞线粒体功能障碍的条件，包括鱼藤酮/抗霉素和高氧刺激，增加转移。MSC-软骨细胞线粒体转移被非特异性和特异性（连接蛋白-43）缝隙连接抑制所阻断。当暴露于机械损伤的软骨时，MSC定位于基质损伤的区域，并将细胞过程深入微裂缝，将线粒体递送至软骨细胞。这项工作提供了深入了解的化学，环境和机械条件，可以引起MSC-软骨细胞线粒体转移在体外和原位，我们的研究结果表明一个新的潜在作用，MSC为基础的治疗软骨损伤后。
Articular cartilage has limited healing capacity and no drugs are available that can prevent or slow the development of osteoarthritis (OA) after joint injury. Mesenchymal stromal cell (MSC)-based regenerative therapies for OA are increasingly common, but questions regarding their mechanisms of action remain. Our group recently reported that although cartilage is avascular and relatively metabolically quiescent, injury induces chondrocyte mitochondrial dysfunction, driving cartilage degradation and OA. MSCs are known to rescue injured cells and improve healing by donating healthy mitochondria in highly metabolic tissues, but mitochondrial transfer has not been investigated in cartilage. Here, we demonstrate that MSCs transfer mitochondria to stressed chondrocytes in cell culture and in injured cartilage tissue. Conditions known to induce chondrocyte mitochondrial dysfunction, including stimulation with rotenone/antimycin and hyperoxia, increased transfer. MSC-chondrocyte mitochondrial transfer was blocked by non-specific and specific (connexin-43) gap-junction inhibition. When exposed to mechanically injured cartilage, MSCs localized to areas of matrix damage and extended cellular processes deep into microcracks, delivering mitochondria to chondrocytes. This work provides insights into the chemical, environmental, and mechanical conditions that can elicit MSC-chondrocyte mitochondrial transfer in vitro and in situ, and our findings suggest a new potential role for MSC-based therapeutics after cartilage injury.
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影响因子：
2.8
作者：
Bartell, Lena R.;Fortier, Lisa A.;Delco, Michelle L.
通讯作者：
Delco, Michelle L.
影响因子：
2.8
作者：
Goetz, Jessica E.;Coleman, Mitchell C.;Fredericks, Douglas C.;Petersen, Emily;Martin, James A.;McKinley, Todd O.;Tochigi, Yuki
通讯作者：
Tochigi, Yuki
影响因子：
4.4
作者：
Blanco, FJ;López-Armada, MJ;Maneiro, E
通讯作者：
Maneiro, E
影响因子：
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作者：
Gavriilidis, Christos;Miwa, Satomi;Young, David A.
通讯作者：
Young, David A.
影响因子：
2.8
作者：
Bonnevie, Edward D.;Delco, Michelle L.;Bonassar, Lawrence J.
通讯作者：
Bonassar, Lawrence J.