Microscale frictional strains determine chondrocyte fate in loaded cartilage.
Microscale frictional strains determine chondrocyte fate in loaded cartilage.
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DOI：
10.1016/j.jbiomech.2018.04.020
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发表时间：
2018-06-06
影响因子：
2.4
通讯作者：
Bonassar LJ
中科院分区：
文献类型：
--
作者：
Bonnevie ED;Delco ML;Bartell LR;Jasty N;Cohen I;Fortier LA;Bonassar LJ
越来越多的证据表明，滑液中润滑剂水平的改变对软骨细胞稳态有急性生物学后果。虽然这些反应与摩擦增加有关，但这种反应背后的机制尚不清楚。在这里，我们将摩擦生物反应器与共聚焦弹性成像和基于图像的细胞分析相结合，以建立软骨摩擦、微尺度剪切应变和急性不良细胞反应之间的联系。我们结合细胞尺度的应变测量结果表明，摩擦升高会在组织表面附近产生高剪切应变，而这些高剪切应变与线粒体功能障碍、细胞凋亡和细胞死亡密切相关。总的来说，我们的数据建立了软骨细胞对摩擦产生负面反应的两种途径：一种是即时的坏死反应，另一种是涉及线粒体功能障碍和细胞凋亡的长期途径。具体而言，在表面区域，剪切应变可超过0.07，细胞易急性死亡；然而，在这个表面区域之下，细胞表现出与局部剪切应变预测的方式一致的凋亡途径。这些数据揭示了软骨细胞损伤由润滑受损引起的机制，并表明除了边界润滑剂外，在关节炎治疗中还有细胞凋亡上游的机会来保持软骨细胞健康。
Mounting evidence suggests that altered lubricant levels within synovial fluid have acute biological consequences on chondrocyte homeostasis. While these responses have been connected to increased friction, the mechanisms behind this response remain unknown. Here, we combine a frictional bioreactor with confocal elastography and image-based cellular assays to establish the link between cartilage friction, microscale shear strain, and acute, adverse cellular responses. Our incorporation of cell-scale strain measurements reveals that elevated friction generates high shear strains localized near the tissue surface, and that these elevated strains are closely associated with mitochondrial dysfunction, apoptosis, and cell death. Collectively, our data establish two pathways by which chondrocytes negatively respond to friction: an immediate necrotic response and a longer term pathway involving mitochondrial dysfunction and apoptosis. Specifically, in the surface region, where shear strains can exceed 0.07, cells are predisposed to acute death; however, below this surface region, cells exhibit a pathway consistent with apoptosis in a manner predicted by local shear strains. These data reveal a mechanism through which cellular damage in cartilage arises from compromised lubrication and show that in addition to boundary lubricants, there are opportunities upstream of apoptosis to preserve chondrocyte health in arthritis therapy.
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影响因子：
--
作者：
RADIN, EL;PAUL, IL
通讯作者：
PAUL, IL
影响因子：
--
作者：
Jay, Gregory D.;Fleming, Braden C.;Watkins, Bryn A.;McHugh, Karen A.;Anderson, Scott C.;Zhang, Ling X.;Teeple, Erin;Waller, Kimberly A.;Elsaid, Khaled A.
通讯作者：
Elsaid, Khaled A.
DOI：
10.1152/ajpheart.00708.2002
发表时间：
2003-02-01
影响因子：
4.8
作者：
Levraut, J;Iwase, H;Schumacker, PT
通讯作者：
Schumacker, PT
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：
2.4
作者：
Carter TE;Taylor KA;Spritzer CE;Utturkar GM;Taylor DC;Moorman CT 3rd;Garrett WE;Guilak F;McNulty AL;DeFrate LE
通讯作者：
DeFrate LE