Inflammatory cytokines and mechanical injury induce post-traumatic osteoarthritis-like changes in a human cartilage-bone-synovium microphysiological system.
Inflammatory cytokines and mechanical injury induce post-traumatic osteoarthritis-like changes in a human cartilage-bone-synovium microphysiological system.
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DOI：
10.1186/s13075-022-02881-z
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发表时间：
2022-08-18
影响因子：
4.9
通讯作者：
中科院分区：
文献类型：
--
作者：
人类外伤性膝关节损伤会立即引起关节组织冲击损伤伴随的滑膜液炎症细胞因子水平的增加。我们建立了一个体外人软骨-骨-滑膜（CBS）共培养模型，以研究机械损伤和炎症在创伤后骨关节炎（pta）样疾病发生中的作用。从16名人类供体（Collin分级0 - 2,23 - 83岁）的25具尸体远端股骨中收获骨软骨塞（软骨-骨，CB）和关节囊滑膜外植体(S)。建立为期两周的单培养(软骨(C)，骨（B)，滑膜(S)）和共培养（CB， CBS）。通过滑膜外植体与机械冲击骨软骨塞（CBS+INJ，峰值应力5MPa）共培养，以无冲击骨软骨塞为对照，建立pta样疾病组。通过分析细胞活力的变化、向培养基释放的炎症细胞因子（10-plex ELISA）、组织基质降解和代谢组学特征来评估疾病样进展。在CBS+INJ和CBS共培养以及S单独培养（IL-1、IL-6、IL-8和TNF-α等）中，炎症细胞因子的浓度立即增加。与未损伤的CB相比，CBS+INJ和CBS也显示软骨细胞死亡增加。CBS和CBS+INJ组向培养基中释放的硫代糖胺聚糖（sGAG）和相关的args -聚集蛋白新表位片段显著增加。在C、B和S单培养中观察到不同的代谢组学特征，并鉴定出与CBS和CB炎症反应相关的代谢物（例如，犬尿氨酸、1-甲基烟酰胺和次黄嘌呤）。CBS和CBS+INJ模型显示与pta样起始/进展相关的明显细胞、炎症和基质相关改变。使用没有OA病史的供体的人类膝关节组织表明，该模型在强调损伤和炎症在pta进展早期阶段的作用方面具有相关性。在线版本包含补充材料，可在10.1186/s13075-022-02881-z获得。
Traumatic knee injuries in humans trigger an immediate increase in synovial fluid levels of inflammatory cytokines that accompany impact damage to joint tissues. We developed a human in vitro cartilage-bone-synovium (CBS) coculture model to study the role of mechanical injury and inflammation in the initiation of post-traumatic osteoarthritis (PTOA)-like disease. Osteochondral plugs (cartilage-bone, CB) along with joint capsule synovium explants (S) were harvested from 25 cadaveric distal femurs from 16 human donors (Collin’s grade 0–2, 23–83years). Two-week monocultures (cartilage (C), bone (B), synovium (S)) and cocultures (CB, CBS) were established. A PTOA-like disease group was initiated via coculture of synovium explants with mechanically impacted osteochondral plugs (CBS+INJ, peak stress 5MPa) with non-impacted CB as controls. Disease-like progression was assessed through analyses of changes in cell viability, inflammatory cytokines released to media (10-plex ELISA), tissue matrix degradation, and metabolomics profile. Immediate increases in concentrations of a panel of inflammatory cytokines occurred in CBS+INJ and CBS cocultures and cultures with S alone (IL-1, IL-6, IL-8, and TNF-α among others). CBS+INJ and CBS also showed increased chondrocyte death compared to uninjured CB. The release of sulfated glycosaminoglycans (sGAG) and associated ARGS-aggrecan neoepitope fragments to the medium was significantly increased in CBS and CBS+INJ groups. Distinct metabolomics profiles were observed for C, B, and S monocultures, and metabolites related to inflammatory response in CBS versus CB (e.g., kynurenine, 1-methylnicotinamide, and hypoxanthine) were identified. CBS and CBS+INJ models showed distinct cellular, inflammatory, and matrix-related alterations relevant to PTOA-like initiation/progression. The use of human knee tissues from donors that had no prior history of OA disease suggests the relevance of this model in highlighting the role of injury and inflammation in earliest stages of PTOA progression. The online version contains supplementary material available at 10.1186/s13075-022-02881-z.
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中等动态压缩抑制软骨对机械损伤，肿瘤坏死因子-α和白介素-6的促代谢反应，但突出了应变阈值以上的降解。
影响因子：
7
作者：
Li, Y.;Frank, E. H.;Wang, Y.;Chubinskaya, S.;Huang, H. -H.;Grodzinsky, A. J.
通讯作者：
Grodzinsky, A. J.
影响因子：
7
作者：
Bajpayee AG;Quadir MA;Hammond PT;Grodzinsky AJ
通讯作者：
Grodzinsky AJ
DOI：
10.1016/0304-4165(86)90306-5
发表时间：
1986-09-04
期刊：
BIOCHIMICA ET BIOPHYSICA ACTA
影响因子：
--
作者：
FARNDALE, RW;BUTTLE, DJ;BARRETT, AJ
通讯作者：
BARRETT, AJ
影响因子：
1.8
作者：
Kafka, V
通讯作者：
Kafka, V
DOI：
10.1249/mss.0000000000002161
发表时间：
2020-03-01
期刊：
MEDICINE AND SCIENCE IN SPORTS AND EXERCISE
影响因子：
--
作者：
Jacobs, Cale A.;Hunt, Emily R.;Lattermann, Christian
通讯作者：
Lattermann, Christian