Enhancement of Matrix Metalloproteinase-2 (MMP-2) as a Potential Chondrogenic Marker during Chondrogenic Differentiation of Human Adipose-Derived Stem Cells.

Yoshie Arai,Jong Lee,Kyoung-Won Ko,Dong-Wook Han,Sunghyun Park,Bogyu Choi,Hun-Kuk Park,Won Choi,Inbo Han,Soo-Hong Lee,Joong-Myung Lee

doi:10.3390/ijms17060963

Abstract

Human adipose-derived stem cells (hASCs) have a capacity to undergo adipogenic, chondrogenic, and osteogenic differentiation. Recently, hASCs were applied to various fields including cell therapy for tissue regeneration. However, it is hard to predict the direction of differentiation of hASCs in real-time. Matrix metalloproteinases (MMPs) are one family of proteolytic enzymes that plays a pivotal role in regulating the biology of stem cells. MMPs secreted by hASCs are expected to show different expression patterns depending on the differentiation state of hASCs because biological functions exhibit different patterns during the differentiation of stem cells. Here, we investigated proteolytic enzyme activity, especially MMP-2 activity, in hASCs during their differentiation. The activities of proteolytic enzymes and MMP-2 were higher during chondrogenic differentiation than during adipogenic and osteogenic differentiation. During chondrogenic differentiation, mRNA expression of MMP-2 and the level of the active form of MMP-2 were increased, which also correlated with Col II. It is concluded that proteolytic enzyme activity and the level of the active form of MMP-2 were increased during chondrogenic differentiation, which was accelerated in the presence of Col II protein. According to our findings, MMP-2 could be a candidate maker for real-time detection of chondrogenic differentiation of hASCs.

Highlights

Human adipose-derived stem cells are used for tissue regeneration because of their potential to undergo various types of differentiation, such as adipogenic, chondrogenic, and osteogenic differentiation [1,2]
To examine the multipotency of Human adipose-derived stem cells (hASCs), three types of differentiation such as adipogenic, chondrogenic, and osteogenic differentiation of hASCs were induced for 21 days with adipogenic medium (AM), chondrogenic medium (CM), and osteogenic medium (OM), respectively
These results indicate the evidence for multipotency of hASCs

Summary

Introduction

Human adipose-derived stem cells (hASCs) are used for tissue regeneration because of their potential to undergo various types of differentiation, such as adipogenic, chondrogenic, and osteogenic differentiation [1,2]. Like other types of stem cells, it is difficult to predict and control the direction of differentiation of hASCs in real-time. By analyzing data obtained from PCR, Western blot, immunohistochemistry, and other analyses, the expression of these markers can be used to evaluate the differentiation state of hASCs. it is still hard to investigate the differentiation potential of hASCs in real-time during differentiation because these analytical methods damage live cells through the isolation of DNA and proteins and, the analysis takes time. It is very critical to evaluate the differentiation of live hASCs in real-time to prepare therapeutic hASCs for clinical applications

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