Immortalization of Cementoblast Progenitor Cells With Bmi-1 and TERT

Saito, Masahiro; Handa, Keisuke; Kiyono, Tohru; Hattori, Shintaro; Yokoi, Takamasa; Tsubakimoto, Takanori; Harada, Hidemitsu; Noguchi, Toshihide; Toyoda, Minoru; Sato, Sadao; Teranaka, Toshio

doi:10.1359/jbmr.2005.20.1.50

Cited by 24 publications

(24 citation statements)

References 40 publications

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“…In the present study, we showed that PLAP-1/asporin expression is markedly enhanced in dental follicle cells of the developing tooth germ. During tooth germ development, progenitor cells present in the dental follicle are believed to play a central role in the formation of periodontal components such as cementum, periodontal ligament, and alveolar bone (25,26). Taken together, PLAP-1/asporin appears to be involved in the formation of periodontal tissues during tooth development.…”

Section: Discussionmentioning

confidence: 99%

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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182

189

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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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Section: Discussionmentioning

confidence: 99%

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

Yamada¹,

Tomoeda²,

Ozawa³

et al. 2007

Journal of Biological Chemistry

Self Cite

182

189

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“…The human periodontal ligament contains multipotent stem cells that differentiate into osteoblasts, cementoblasts, and fibroblasts, and these cells could possibly be used to induce periodontal regeneration (Seo et al 2004(Seo et al ,2005. Additionally, the dental follicle has been utilized as a source of undifferentiated cells in in vitro and in vivo studies (Saito et al 2005). Because the dental follicle and periodontal ligament are immunopositive for periostin (Kruzynska-Frejtag et al 2004;Suzuki et al 2004), this protein is often used as a marker of these tissues.…”

mentioning

confidence: 99%

Immunohistochemical Localization of α-Smooth Muscle Actin During Rat Molar Tooth Development

Hosoya

Nakamura

Ninomiya

et al. 2006

J Histochem Cytochem.

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The dental follicle contains mesenchymal cells that differentiate into osteoblasts, cementoblasts, and fibroblasts. However, the characteristics of these mesenchymal cells are still unknown. α-Smooth muscle actin (α-SMA) is known to localize in stem cells and precursor cells of various tissues. In the present study, to characterize the undifferentiated cells in the dental follicle, immunohistochemical localization of α-SMA was examined during rat molar tooth development. Rat mandibles were collected at embryonic days (E) 15-20 and postnatal days (P) 7-28. Immunohistochemical stainings for α-SMA, periostin, Runt-related transcription factor-2 (Runx2), tissue nonspecific alkaline phosphatase (TNAP), and bone sialoprotein (BSP) were carried out using paraffin-embedded sections. α-SMA localization was hardly detected in the bud and cap stages. At the early bell stage, α-SMA-positive cells were visible in the dental follicle around the cervical loop. At the late bell to early root formation stage (P14), these cells were detected throughout the dental follicle, but they were confined to the apical root area at P28. Double immunostaining for α-SMA and periostin demonstrated that α-SMA-positive cells localized to the outer side of periostin-positive area. Runx2-positive cells were visible in the α-SMA-positive region. TNAP-positive cells in the dental follicle localized nearer to alveolar bone than Runx2-positive cells. BSP was detected in osteoblasts as well as in alveolar bone matrix. These results demonstrate that α-SMA-positive cells localize on the alveolar bone side of the dental follicle and may play a role in alveolar bone formation.

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“…These findings suggest that important regulator genes for osteosarcoma growth may be hypermethylated. BMI-1 co-overexpression with other inducers, such as H-RAS, hTERT and p16 INK4a shRNA, resulted in efficient malignant transformation (36,40,41,44). These findings in turn suggest that other factors might be regulated in addition to BMI-1 to suppress osteosarcoma growth.…”

Section: Discussionmentioning

confidence: 87%

“…It has been reported that overexpression of EZH2 or BMI-1 promotes malignant transformation (21,36,38,(40)(41)(42)(43)(44)(45)(46)(47). In addition, inhibition of EZH2 or BMI-1 inhibits growth of various types of malignancies (38,41,43,45,46).…”

Section: Knock-down Of Overexpressed Ezh2 and Bmi-1 Does Not Prevent mentioning

confidence: 99%

The knock-down of overexpressed EZH2 and BMI-1 does not prevent osteosarcoma growth

Sasaki

Setoguchi²,

Matsunoshita³

et al. 2010

Oncol Rep

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Abstract. Polycomb group proteins control the transcriptional memory of cells by maintaining the stable silencing of specific sets of genes through chromatin modifications. Polycomb group protein complexes control gene repression through recruitment of histone deacetylase. This recruitment leads to trimethylation of Lys 27 of histone H3 (H3K27). Histone H3K27 trimethylation is a property of stably silenced heterochromatin. EZH2 and BMI-1 are pivotal components of polycomb group protein complexes. Increased EZH2 levels have been found in several malignancies and reported as a molecular biomarker of poor prognosis. Similarly, BMI-1 has also been found to be associated with malignant transformation. In addition, inhibition of EZH2 or BMI-1 inhibits the growth of various types of malignancies. The expression of BMI-1 and EZH2 in human osteosarcoma has not been clearly determined. We examined the potential involvement of aberrant polycomb group protein expression in the pathogenesis of osteosarcoma. Real-time PCR revealed that expression of EZH2 in 143B, HOS, NOS-1 and Saos2 was increased compared to normal osteoblasts. BMI-1 was also up-regulated in 143B, HOS and NOS-1. Expression of EZH2 and BMI-1 were up-regulated in osteosarcoma patient biopsy specimens compared to normal bone. Immunohistochemical examinations showed that EZH2 and BMI-1 were up-regulated in osteosarcoma cells and that trimethylation of histone H3K27 was increased. We examined the effects of knock down of EZH2 and BMI-1 by shRNA. Unexpectedly, the knock-down of EZH2 and BMI-1 did not prevent osteosarcoma growth either in vitro or in vivo. Our findings suggest that EZH2 and BMI-1 may be tumorassociated antigens of osteosarcoma, but are not useful molecular targets of osteosarcoma treatment.

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Immortalization of Cementoblast Progenitor Cells With Bmi-1 and TERT

Cited by 24 publications

References 40 publications

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

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

Immunohistochemical Localization of α-Smooth Muscle Actin During Rat Molar Tooth Development

The knock-down of overexpressed EZH2 and BMI-1 does not prevent osteosarcoma growth

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