Inhibition of interleukin-1beta-stimulated dedifferentiation of chondrocytes via controlled release of CrmA from hyaluronic acid-chitosan microspheres.
Inhibition of interleukin-1beta-stimulated dedifferentiation of chondrocytes via controlled release of CrmA from hyaluronic acid-chitosan microspheres.
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DOI：
10.1186/s12891-015-0521-6
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发表时间：
2015-03-18
影响因子：
2.3
通讯作者：
Wang Q
中科院分区：
文献类型：
--
作者：
Ma BL;Zhou PH;Xie T;Shi L;Qiu B;Wang Q
既往研究表明CrmA可改善IL-1β诱导的骨关节炎。本研究探讨了透明质酸（HA）-壳聚糖（CS）微球中细胞因子反应调节剂A（CrmA）的控释对白细胞介素-1 β（IL-1β）诱导的软骨细胞去分化的影响。以10 ng/ml的IL-1β为调节剂和软骨细胞诱导剂，建立大鼠骨关节炎（OA）体外模型。IL-1β与新鲜分离的大鼠软骨细胞共培养48 h后，加入HA CS CrmA微球。测定软骨细胞活力和糖胺聚糖（GAG）含量。酶联免疫吸附试验（ELISA）检测CrmA的分泌水平。Western blotting法检测各组细胞中II型胶原、聚集蛋白聚糖、I型胶原和IL-1β的表达。CrmA释放动力学的特征在于初始突释，其在十天内减少到线性释放。与对照组相比，GAG的产生和II型胶原、聚集蛋白聚糖的表达明显增加，而I型胶原和IL-1β的表达减少。本研究表明，含有CrmA的HA-CS微球可以通过在培养扩增期间保持软骨细胞的表型来减轻关节软骨的退变。抑制关节内炎性细胞因子的活性可能是微球治疗OA的重要机制之一。
The previous studies indicated that CrmA could ameliorate the interleukin-1β induced osteoarthritis. In this study, we investigated the controlled-released cytokine response modifier A (CrmA) from hyaluronic acid (HA)-chitosan (CS) microspheres to improve interleukin-1β (IL-1β)-stimulated dedifferentiation of chondrocytes. A rat model of osteoarthritis (OA) in vitro was established using 10 ng/ml IL-1β as modulating and chondrocytes inducing agent. HA-CS-CrmA microspheres were added to the medium after IL-1β was co-cultured with freshly isolated rat chondrocytes for 48 hours. The chondrocytes viability and glycosaminoglycan (GAG) content were determined. The level of CrmA secreted was detected by Enzyme-Linked Immunosorbent Assay (ELISA). The protein levels of type II collagen, aggrecan, collagen I and IL-1β were detected using western blotting analyses. The CrmA release kinetics were characterized by an initial burst release, which was reduced to a linear release over ten days. The production of GAG and the expression of type II collagen, aggrecan significantly increased compared with the control group, while the expression of collagen I and IL-1β decreased. This study demonstrated that HA-CS microspheres containing CrmA could attenuate the degeneration of articular cartilage by maintaining the phenotype of chondrocytes during culture expansion. The suppression of inflammatory cytokines activity within the joint might be one important mechanism of the action of the microspheres in the treatment of OA.
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DOI：
10.1084/jem.189.1.131
发表时间：
1999-01-04
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
MacDonald G;Shi L;Vande Velde C;Lieberman J;Greenberg AH
通讯作者：
Greenberg AH
影响因子：
5.1
作者：
Fujino, M;Kawasaki, M;Li, XK
通讯作者：
Li, XK
影响因子：
10.8
作者：
Ito, Tomoko;Iida-Tanaka, Naoko;Koyama, Yoshiyuki
通讯作者：
Koyama, Yoshiyuki
影响因子：
14
作者：
Forsey, Richard W.;Fisher, John;Ingham, Eileen
通讯作者：
Ingham, Eileen
影响因子：
--
作者：
Julovi, SM;Yasuda, T;Nakamura, T
通讯作者：
Nakamura, T