The degradation of chondrogenic pellets using cocultures of synovial fibroblasts and U937 cells.
The degradation of chondrogenic pellets using cocultures of synovial fibroblasts and U937 cells.
复制标题
DOI：
10.1016/j.biomaterials.2013.10.050
复制
发表时间：
2014-01
期刊：
影响因子：
14
通讯作者：
Kaplan, David L.
中科院分区：
文献类型：
--
作者：
Blasioli, Dominick J.;Matthews, Gloria L.;Kaplan, David L.
膝关节骨关节炎（OA）的特征通常是X线显示的关节间隙狭窄、膝关节疼痛以及通过进行性软骨退化和间歇性滑膜炎症导致的关节功能丧失。这项工作的目的是在临床相关系统中开发体外模型。将正常人滑膜成纤维细胞与U937细胞一起培养3天，然后再与软骨形成干细胞沉淀物组合4天。该培养系统模拟了早期OA的许多方面，包括细胞因子和降解酶MMP-1和MMP-3的产生，从而产生类似于OA滑液的条件培养基谱。这种分解代谢环境导致糖胺聚糖（GAG）从颗粒中释放。以与早期OA类似的方式，团块具有增加的聚集蛋白聚糖和胶原II表达。所有这些影响都是早期OA的标志。这种相对简单的组织模型包含与滑膜细胞和巨噬细胞相互作用的3D软骨成分，可能有助于了解OA的早期原因和进展。它可以容易地缩放，因此可用于在临床相关系统中高通量筛选疾病修饰药物。
Osteoarthritis (OA) of the knee is often characterized by joint space narrowing on X-ray, knee pain, and a loss of joint function through progressive cartilage degradation and intermittent synovial inflammation. The objective of this work was to develop an in vitro model in a clinically relevant system. Normal human synovial fibroblasts were cultured with U937 cells for 3 days then combined with a chondrogenic stem cell pellet for another 4 days. This culture system mimicked many of the aspects of early stage OA including production of cytokines and degradative enzymes, MMP-1 and MMP-3, resulting in a conditioned medium profile similar to OA synovial fluid. This catabolic environment resulted in the release of glycosaminoglycan (GAG) from the pellet. In a similar manner to early stage OA, the pellet had increased aggrecan and collagen II expression. All of these effects are hallmarks of early stage OA. This relatively simple tissue model containing a 3D cartilage component interacting with synoviocytes and macrophages could be useful to understand early causes and progression of OA. It can be scaled easily thus useful for high throughput screening of disease modifying drugs in a clinically relevant system.
登录
查看更多内容
影响因子：
--
作者：
Lawrence, Reva C.;Felson, David T.;Wolfe, Frederick
通讯作者：
Wolfe, Frederick
影响因子：
27.4
作者：
Freemont, AJ;Hampson, V;Hoyland, JA
通讯作者：
Hoyland, JA
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：
--
作者：
Agarwal, Sandeep K.;Lee, David M.;Brenner, Michael B.
通讯作者：
Brenner, Michael B.
影响因子：
6.4
作者：
Fleischer, J;Soeth, E;Ernst, M
通讯作者：
Ernst, M