Collaborative action of M-CSF and CTGF/CCN2 in articular chondrocytes: Possible regenerative roles in articular cartilage metabolism
Collaborative action of M-CSF and CTGF/CCN2 in articular chondrocytes: Possible regenerative roles in articular cartilage metabolism
复制标题
DOI：
10.1016/j.bone.2004.10.015
复制
发表时间：
2005-05-01
期刊：
影响因子：
4.1
通讯作者：
Takigawa, M
中科院分区：
文献类型：
--
作者：
Nakao, K;Kubota, S;Takigawa, M
已知巨噬细胞集落刺激因子（M-CSF）基因的表达在炎症时在关节软骨细胞中被诱导。然而，M-CSF在软骨中的功能作用尚不清楚。在这项研究中，我们描述了M-CSF在保护和维护关节软骨的基础上，使用人软骨细胞和大鼠原代软骨细胞的实验结果的可能作用。结缔组织生长因子（CTGF/CCN 2）是一种通过促进关节软骨细胞的生长和分化来再生受损软骨的有效分子。在此，我们发现M-CSF诱导这些细胞中ctgf/ccn 2基因的mRNA表达的事实。还证实了M-CSF增强CTGF/CCN 2蛋白的产生。此外，M-CSF可以自动激活m-CSF基因，形成正反馈网络，以放大和延长所观察到的效果。最后，通过加入M-CSF观察到蛋白聚糖合成的促进作用。这些发现共同表明M-CSF与CTGF/CCN 2合作在关节软骨代谢中的新作用，特别是在炎症反应期间。这种作用的M-CSF进一步支持的分布M-CSF产生的软骨细胞在实验诱导的大鼠骨关节炎软骨在体内。(c)2004年爱思唯尔公司All rights reserved.
It is known that expression of the macrophage colony-stimulating factor (M-CSF) gene is induced in articular chondrocytes upon inflammation. However, the functional role of M-CSF in cartilage has been unclear. In this study, we describe possible roles of M-CSF in the protection and maintenance of the articular cartilage based on the results of experiments using human chondrocytic cells and rat primary chondrocytes. Connective tissue growth factor (CTGF/CCN2) is known to be a potent molecule to regenerate damaged cartilage by promoting the growth and differentiation of articular chondrocytes. Here, we uncovered the fact that M-CSF induced the mRNA expression of the ctgf/ccn2 gene in those cells. Enhanced production of CTGF/CCN2 protein by M-CSF was also confirmed. Furthermore, M-CSF could autoactivate the m-csf gene, forming a positive feed-back network to amplify and prolong the observed effects. Finally, promotion of proteoglycan synthesis was observed by the addition of M-CSF. These findings taken together indicate novel roles of M-CSF in articular cartilage metabolism in collaboration with CTGF/CCN2, particularly during an inflammatory response. Such roles of M-CSF were further supported by the distribution of M-CSF producing chondrocytes in experimentally induced rat osteoarthritis cartilage in vivo. (c) 2004 Elsevier Inc. All rights reserved.