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Differential MMP-2 Activity Induced by Mechanical Compression and Inflammatory Factors in Human Synoviocytes

Yequan Wang*, Li Yang*, Jin Zhang*, Ruyue Xue*, Zhenyu Tang*, Wei Huang, Dianming Jiang, Xinyan Tang*, Peter Chen, KL Paul Sung∗,‡,§,¶
* “111”project Laboratory of Biomechanics and Tissue Repair, College of Bioengineering, Chongqing University, Chongqing 400044, China
Department of Orthopaedics, Chongqing University of Medical Sciences, Chongqing,China
Departments of Bioengineering, University of California, San Diego, 9500Gilman Drive, La Jolla, CA 92093-0412, USA
§ Department of Orthopaedics,UCSD
Correspondence author. College of Bioengineering, Chongqing University, Chongqing 400044, China. E-mail: klsung@ucsd.edu

Molecular & Cellular Biomechanics 2010, 7(2), 105-114. https://doi.org/10.3970/mcb.2010.007.105

Abstract

The anterior cruciate ligament, posterior cruciate ligament, cartilage and meniscus in human knee joint have poor healing ability. Accumulation of MMPs in the joint fluids due to knee injury has been considered as the main reason. Our previous experiments showed that synovium may be the major regulator of MMPs in joint cavity after injury. In this paper, we used human synoviocytes harvested from synovium to determine whether mechanical injury and inflammatory factors will induce MMP-2 production in synoviocytes. With zymography, we found that mechanical compression increased the MMP-2 production by 23% under 6% compressions, 61% under 12% compression and 109% under 14% compressions. In addition, TNF-acan also elevate the activity of MMP-2 in a dose dependent manner, while IL-1α does not. However, mixture of these two factors dramatically increased MMP-2 production by 201%. In addition, mechanical injury had a strong synergistic effect on MMP-2 production with TNF-α, IL-1α and their mixture, increasing by 207%, 354% and 468% individually. The generic MMP activity assay revealed that mechanical compression increased the generic activity. APMA treatment increased the generic activity of MMPs induced by compression but not inflammatory factors, which indicates that compression would induce MMPs in pro-form while inflammatory factors induce MMPs mostly in active-form. We concluded that mechanical injury and inflammation would induce large amount of MMP-2 and global MMP activity in synoviocytes, which is always injured accompanied by the injury of other joint tissues. The accumulation of MMPs and the elevated proteolytic activities in the comparative isolated joint cavity would destroy the balance of tissue repairs, which may be the major reason why joint tissues have poor healing ability. Thus, synvoium may be involved in regulating the micro-environment of joint cavity and the injury/healing process of knee joint tissue.

Keywords

Synoviocytes, compression, TNF-α, IL-1α, MMP-2

Cite This Article

Wang, Y., Yang, L., Zhang, J., Xue, R., Tang, Z. et al. (2010). Differential MMP-2 Activity Induced by Mechanical Compression and Inflammatory Factors in Human Synoviocytes. Molecular & Cellular Biomechanics, 7(2), 105–114.



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