Expression profile of active genes in human periodontal ligament and isolation of PLAP-1, a novel SLRP family gene

Yamada, Satoru; Murakami, Shinya; Matoba, Ryo; Ozawa, Yasuhiro; Yokokoji, Takayoshi; Nakahira, Yo; Ikezawa, Kazuhiko; Takayama, S.; Matsubara, Kazuo; Okada, Hiroshi

doi:10.1016/s0378-1119(01)00683-7

Cited by 84 publications

(86 citation statements)

References 13 publications

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“…Our data have demonstrated that the transcription of PLAP-1 was upregulated during the process of cytodifferentiation of PDL cells into mineralized-tissue-forming cells (Fig. 8A), which is consistent with previous studies (6). Moreover, we established an expression profile of miRNAs targeting the PLAP-1 gene in human PDLCs and identified the differential expression patterns of miRNAs closely associated with the process of osteogenic differentiation of PDLCs for the first time.…”

Section: Discussionsupporting

confidence: 91%

“…Periodontal ligament associated protein-1 (PLAP-1/ asporin), a specific marker of the PDL, is an important negative regulator of osteogenic differentiation in maintaining the homeostasis of periodontium (6)(7)(8). PLAP-1 was first identified as a novel member of the small leucine-rich repeat proteoglycan (SLRP) family and confirmed to be expressed specifically and predominantly in the PDL (9-10).…”

Section: Introductionmentioning

confidence: 99%

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miR-21 and miR-101 regulate PLAP-1 expression in periodontal ligament cells

Yue

et al. 2012

Mol Med Report

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Abstract. Periodontal ligament-associated protein-1 (PLAP-1/ asporin) is a special marker in periodontal ligament tissue. It is an important regulator of osteogenic differentiation of periodontal ligament cells (PDLCs). This marker is also a prerequisite for periodontal ligament development and mineralization in maintaining homeostasis of the periodontium. However, the molecular mechanisms of the regulation of PLAP-1 expression at the post-transcriptional level remain unknown. By contrast, microRNAs (miRNAs) provide an additional level of regulation beyond that of transcription factors via regulation of the post-transcriptional control of gene expression. This study was designed to analyze miRNA differential expression patterns of PDLCs at various osteoblastic differentiation stages and to determine the contribution of miRNAs in the regulation of PLAP-1 expression during osteoblast differentiation. Bioinformatic analysis was performed to predict miRNAs that potentially regulate the gene expression of PLAP-1. Dual luciferase reporter assay and qRT-PCR were performed to confirm the effects of these miRNAs on PLAP-1 gene expression. Our results indicated that mir-101 and mir-21 target PLAP-1 to regulate its expression during osteogenic differentiation of PDLCs. IntroductionPeriodontal ligament (PDL), the most important tissue influencing the lifespan of the human tooth, is composed of heterogeneous cell populations including osteoblasts, which have osteogenic differentiation potential (1-3). Osteogenesis of periodontal ligament cells (PDLCs) is part of an important process of cytodifferentiation and mineralization to form mineralized tissue cells (4). Osteoblast differentiation results in the expression of tissue-specific gene products that form and regulate the structure of the mineralized PDL extracellular matrix (5).Periodontal ligament associated protein-1 (PLAP-1/ asporin), a specific marker of the PDL, is an important negative regulator of osteogenic differentiation in maintaining the homeostasis of periodontium (6-8). PLAP-1 was first identified as a novel member of the small leucine-rich repeat proteoglycan (SLRP) family and confirmed to be expressed specifically and predominantly in the PDL (9-10). PLAP-1 was found to be closely associated with the process of cytodifferentiation of PDL cells (11). Therefore, the relative expression level of PLAP-1 may be regarded as a specific marker for the osteogenic differentiation of PDLCs.Moreover, PLAP-1 was not only expressed specifically in the PDL of an erupted tooth but also in the dental follicle, which is the progenitor tissue of the PDL during tooth development (8). This result suggests that PLAP-1 may be involved in PDL development and cytodifferentiation (11).Furthermore, it is important to understand the processes that regulate the mineralization of PDLCs. Previous studies showed that the osteogenesis of PDLCs, a complex process in which multiple signaling pathways are involved, is regulated by numerous growth and transcription factors (12-14). However, the...

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Section: Discussionsupporting

confidence: 91%

Section: Introductionmentioning

confidence: 99%

miR-21 and miR-101 regulate PLAP-1 expression in periodontal ligament cells

Yue

et al. 2012

Mol Med Report

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“…1A). Our previous study showed dom-inant expression of PLAP-1/asporin in human PDL tissue (6). On the other hand, PLAP-1/asporin mRNA has been shown to be expressed abundantly in the heart in both mice and humans (7,8).…”

Section: Specific Expression Of Plap-1/asporin In the Periodontalmentioning

confidence: 95%

“…Previously we have reported the gene expression profile, described the quantitative aspects of the genes active in the human PDL, and identified a novel gene, PLAP-1, that is frequently expressed in human PDL tissue (6). An identical gene has been reported by other groups and named asporin because of its unique aspartic acid repeat at the N terminus of the mature protein (7,8).…”

Section: Periodontal Ligament (Pdl)mentioning

confidence: 96%

PLAP-1/Asporin, a Novel Negative Regulator of Periodontal Ligament Mineralization

Yamada¹,

Tomoeda²,

Ozawa³

et al. 2007

Journal of Biological Chemistry

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185

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Periodontal ligament-associated protein-1 (PLAP-1)/asporin is a recently identified novel member of the small leucine-rich repeat proteoglycan family. PLAP-1/asporin is involved in chondrogenesis, and its involvement in the pathogenesis of osteoarthritis has been suggested. We report that PLAP-1/asporin is also expressed specifically and predominantly in the periodontal ligament (PDL) and that it negatively regulates the mineralization of PDL cells. In situ hybridization analysis revealed that PLAP-1/asporin was expressed specifically not only in the PDL of an erupted tooth but also in the dental follicle, which is the progenitor tissue of the PDL during tooth development. Overexpression of PLAP-1/asporin in mouse PDL-derived clone cells interfered with both naturally and bone morphogenetic protein 2 (BMP-2)-induced mineralization of the PDL cells. On the other hand, knockdown of PLAP-1/asporin transcript levels by RNA interference enhanced BMP-2-induced differentiation of PDL cells. Furthermore co-immunoprecipitation assays showed a direct interaction between PLAP-1/asporin and BMP-2 in vitro, and immunohistochemistry staining revealed the co-localization of PLAP-1/asporin and BMP-2 at the cellular level. These results suggest that PLAP-1/ asporin plays a specific role(s) in the periodontal ligament as a negative regulator of cytodifferentiation and mineralization probably by regulating BMP-2 activity to prevent the periodontal ligament from developing non-physiological mineralization such as ankylosis.

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“…PDL cell populations include fibroblasts, which are principal cells in PDL tissue (Berkovitz et al, 1995;Beertsen et al, 1997), undifferentiated mesenchymal cells, epithelial cell rests of Malassez and endothelial cells. PDL cells not only produce collagen fibers and other ECM proteins, but have osteoblastic/cementoblastic properties (Roberts et al, 1982;McCulloch et al, 1991), such as high alkaline phosphatase (ALP) activity (Lekic et al, 1996) and the expression of osteoblastrelated genes, including Runt-related transcription factor-2 (Fujii et al, 2006), Osterix (Kato et al, 2005), bone sialoprotein (Lekic et al, 2001), osteopontin (Chutivongse et al, 2005), osteocalcin ) and periostin (Yamada et al, 2001). Additionally, PDL cells synthesize an osteoclastogenesis activator, receptor activator of NF-kappa B ligand (Kanzaki et al, 2001), as well as its inhibitor, osteoprotegerin (Wada et al, 2001;Hasegawa et al, 2002), suggesting that these cells participate in alveolar bone metabolism.…”

Section: What Are Pdl Tissues and What Are Their Roles?mentioning

confidence: 99%