Jeon June E, Schrobback Karsten, Meinert Christoph, Sramek Viviana, Hutmacher Dietmar W, Klein Travis J
Queensland University of Technology, Brisbane, Queensland, Australia.
Arthritis Rheum. 2013 Sep;65(9):2356-67. doi: 10.1002/art.38049.
One of the pathologic changes that occurs during osteoarthritis (OA) is the degeneration of the pericellular matrix (PCM). Since the PCM is likely to be involved in mechanotransduction, this study was undertaken to investigate the effects of PCM-like matrix accumulation in zonal OA chondrocytes and their influence on chondrocyte response to compression.
Superficial and middle/deep zone chondrocytes from macroscopically normal cartilage of OA knees were expanded and encapsulated in alginate gels. The effects of compression (short-term or long-term) and preculture on chondrocyte expression of various matrix molecules, cytokines, and matrix metalloproteinases (MMPs) were assessed. Additionally, nonexpanded chondrocytes were encapsulated in alginate and cultured in the presence or absence of transforming growth factor β1 (TGFβ1) and dexamethasone and analyzed following short-term compression experiments.
Expanded OA chondrocytes (superficial and middle/deep zone) that were precultured for 2 weeks under free-swelling conditions prior to dynamic compression responded more sensitively to loading and had increased matrix accumulation, increased interleukin-1β (IL-1β) and IL-4 levels, and decreased levels of MMP-2 (in the middle/deep zone) compared to the nonloaded controls. Compression also decreased MMP-3 and MMP-13 levels even without preculture. Nonexpanded chondrocytes did not respond to compression, but differences in gene expression were found depending on the zone of harvest, time in culture, and medium composition.
Our findings demonstrate that with predeposited PCM-like matrix, compressive stimulation can enhance matrix protein accumulation in expanded OA chondrocytes. Investigations into how PCM or other matrix components differentially affect this balance under mechanical loading may provide invaluable insight into OA pathogenesis and the use of expanded cells in tissue engineering and regenerative medicine-based applications.
骨关节炎（OA）发生过程中的病理变化之一是细胞周围基质（PCM）的退变。由于PCM可能参与机械转导，因此开展本研究以探究类PCM基质在OA带区软骨细胞中的积聚效应及其对软骨细胞压缩反应的影响。
从OA膝关节宏观正常软骨中获取表层和中/深层软骨细胞，进行扩增并包封于藻酸盐凝胶中。评估压缩（短期或长期）及预培养对软骨细胞各种基质分子、细胞因子和基质金属蛋白酶（MMPs）表达的影响。此外，将未扩增的软骨细胞包封于藻酸盐中，在有或无转化生长因子β1（TGFβ1）和地塞米松的情况下进行培养，并在短期压缩实验后进行分析。
与未加载的对照组相比，在动态压缩前于自由肿胀条件下预培养2周的扩增OA软骨细胞（表层和中/深层）对加载反应更敏感，基质积聚增加，白细胞介素-1β（IL-1β）和IL-4水平升高，MMP-2水平降低（中/深层）。即使未进行预培养，压缩也会降低MMP-3和MMP-13水平。未扩增的软骨细胞对压缩无反应，但根据收获区域、培养时间和培养基组成发现基因表达存在差异。
我们的研究结果表明，对于预沉积类PCM基质，压缩刺激可增强扩增OA软骨细胞中的基质蛋白积聚。研究PCM或其他基质成分在机械负荷下如何差异影响这种平衡，可能为OA发病机制以及在基于组织工程和再生医学的应用中使用扩增细胞提供宝贵的见解。
