Abstract
Periodontal ligament (PDL) stem cells (PDLSCs) have been reported as a useful cell source for periodontal tissue regeneration. However, one of the issues is the difficulty of obtaining a sufficient number of PDLSCs for clinical application because very few PDLSCs can be isolated from PDL tissue of donors. Therefore, we aimed to identify a specific factor that converts human PDL cells into stem-like cells. In this study, microarray analysis comparing the gene profiles of human PDLSC lines (2-14 and 2-23) with those of a cell line with a low differentiation potential (2-52) identified the imprinted gene mesoderm-specific transcript (MEST). MEST was expressed in the cytoplasm of 2-23 cells. Knockdown of MEST by siRNA in 2-23 cells inhibited the expression of stem cell markers, such as CD105, CD146, p75NTR, N-cadherin, and NANOG; the proliferative potential; and multidifferentiation capacity for osteoblasts, adipocytes, and chondrocytes. On the other hand, overexpression of MEST in 2-52 cells enhanced the expression of stem cell markers and PDL-related markers and the multidifferentiation capacity. In addition, MEST-overexpressing 2-52 cells exhibited a change in morphology from a spindle shape to a stem cell-like round shape that was similar to 2-14 and 2-23 cell morphologies. These results suggest that MEST plays a critical role in the maintenance of stemness in PDLSCs and converts PDL cells into PDLSC-like cells. Therefore, this study indicates that MEST may be a therapeutic factor for periodontal tissue regeneration by inducing PDLSCs.
Highlights
The periodontal ligament (PDL) is a fiber-rich connective tissue located between the alveolar bone and cementum covering the tooth root, which plays important roles in tooth support as well as nutrition, protection from bacterial attack, sensory input for mastication, and homeostasis [1,2,3,4]
To identify the specific factor for human PDL stem cells (PDLSCs), we conducted microarray analysis to compare gene expression among three human PDL cell lines, 2-14, 2-23, and 2-52. 2-52 cells exhibited a spindle-like shape, while 2-14 and 2-23 cells exhibited a somewhat rounded shape (Figure 1(a)). 2-14 and 2-23 cells possessed a multidifferentiation capacity for osteoblasts, adipocytes, and chondrocytes, whereas 2-52 cells exhibited a limited differentiation capacity (Figure 1(b)). 2-14 and 2-23 cells highly expressed the mesenchymal stem cell (MSC) surface markers, such as CD105 and CD146 (Figure 1(c) and Supplemental Figure 1a), and stem cell-related markers, such as p75NTR, N-cadherin, and NANOG (Figure 1(d)), whereas 2-52 cells expressed fewer of these stem cell markers than 2-14 and 2
Based on the results of microarray analysis (2-14 vs. 2-52 and 2-23 vs. 2-52), we selected the molecules that were highly expressed in both human PDLSC lines and focused on mesoderm-specific transcript (MEST) (Figure 1(f))
Summary
The periodontal ligament (PDL) is a fiber-rich connective tissue located between the alveolar bone and cementum covering the tooth root, which plays important roles in tooth support as well as nutrition, protection from bacterial attack, sensory input for mastication, and homeostasis [1,2,3,4]. Previous reports have indicated that human PDL tissue contains somatic stem cells [6]. These cells termed as PDL stem cells (PDLSCs) express mesenchymal stem cell (MSC) surface markers, such as CD105 and CD146 [6,7,8,9,10], and various stem cell-related markers, such as p75NTR (the neural crest marker) [10, 11], N-cadherin (the mesenchymal stem cell marker) [10], and NANOG PDLSCs display a multidifferentiation capacity for osteoblasts, adipocytes, and chondrocytes in vitro to MSCs [6, 14] and possess the capacity to generate cementum- and PDL-like tissues in vivo [6]. Because the percentage of resident stem cells in PDL tissue is very low [17] and isolation of PDLSCs involves tooth extraction, it has been difficult to stably obtain sufficient PDLSCs for research and clinical applications
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