Endoglin is involved in BMP-2-induced osteogenic differentiation of periodontal ligament cells through a pathway independent of Smad-1/5/8 phosphorylation

Osamu Ishibashi, Mika Ikegame, Fumio Takizawa, Tatsuya Yoshizawa, Md Ali Moksed, Futabako Iizawa, Hisashi Mera, Akio Matsuda, Hiroyuki Kawashima

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

The periodontal ligament (PDL), a connective tissue located between the cementum of teeth and the alveolar bone of mandibula, plays a crucial role in the maintenance and regeneration of periodontal tissues. The PDL contains fibroblastic cells of a heterogeneous cell population, from which we have established several cell lines previously. To analyze characteristics unique for PDL at a molecular level, we performed cDNA microarray analysis of the PDL cells versus MC3T3-E1 osteoblastic cells. The analysis followed by validation by reverse transcription-polymerase chain reaction and immunochemical staining revealed that endoglin, which had been shown to associate with transforming growth factor (TGF)-b and bone morphogenetic proteins (BMPs) as signaling modulators, was abundantly expressed in PDL cells but absent in osteoblastic cells. The knockdown of endoglin greatly suppressed the BMP-2-induced osteoblastic differentiation of PDL cells and subsequent mineralization. Interestingly, the endoglin knockdown did not alter the level of Smad-1/5/8 phosphorylation induced by BMP-2, while it suppressed the BMP-2-induced expression of Id1, a representative BMP-responsive gene. Therefore, it is conceivable that endoglin regulates the expression of BMP-2-responsive genes in PDL cells at some site downstream of Smad-1/5/8 phosphorylation. Alternatively, wefound that Smad-2 aswell as Smad-1/5/8was phosphorylated by BMP-2 in the PDL cells, and that the BMP-2-induced Smad-2 phosphorylation was suppressed by the endoglin knockdown. These results, taken together, raise a possibility that PDL cells respond to BMP-2 via a unique signaling pathway dependent on endoglin, which is involved in the osteoblastic differentiation and mineralization of the cells.

Original languageEnglish
Pages (from-to)465-473
Number of pages9
JournalJournal of Cellular Physiology
Volume222
Issue number2
DOIs
Publication statusPublished - Feb 2010

Fingerprint

Bone Morphogenetic Protein 2
Periodontal Ligament
Phosphorylation
Ligaments
Bone Morphogenetic Proteins
Genes
Cells
Tissue
Endoglin
Dental Cementum
Polymerase chain reaction
Transforming Growth Factors
Transcription
Microarrays
Microarray Analysis
Modulators
Oligonucleotide Array Sequence Analysis
Connective Tissue
Bone
Reverse Transcription

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Cell Biology
  • Physiology

Cite this

Endoglin is involved in BMP-2-induced osteogenic differentiation of periodontal ligament cells through a pathway independent of Smad-1/5/8 phosphorylation. / Ishibashi, Osamu; Ikegame, Mika; Takizawa, Fumio; Yoshizawa, Tatsuya; Moksed, Md Ali; Iizawa, Futabako; Mera, Hisashi; Matsuda, Akio; Kawashima, Hiroyuki.

In: Journal of Cellular Physiology, Vol. 222, No. 2, 02.2010, p. 465-473.

Research output: Contribution to journalArticle

Ishibashi, Osamu ; Ikegame, Mika ; Takizawa, Fumio ; Yoshizawa, Tatsuya ; Moksed, Md Ali ; Iizawa, Futabako ; Mera, Hisashi ; Matsuda, Akio ; Kawashima, Hiroyuki. / Endoglin is involved in BMP-2-induced osteogenic differentiation of periodontal ligament cells through a pathway independent of Smad-1/5/8 phosphorylation. In: Journal of Cellular Physiology. 2010 ; Vol. 222, No. 2. pp. 465-473.
@article{387125fde7a04c49806129d3cd1ee659,
title = "Endoglin is involved in BMP-2-induced osteogenic differentiation of periodontal ligament cells through a pathway independent of Smad-1/5/8 phosphorylation",
abstract = "The periodontal ligament (PDL), a connective tissue located between the cementum of teeth and the alveolar bone of mandibula, plays a crucial role in the maintenance and regeneration of periodontal tissues. The PDL contains fibroblastic cells of a heterogeneous cell population, from which we have established several cell lines previously. To analyze characteristics unique for PDL at a molecular level, we performed cDNA microarray analysis of the PDL cells versus MC3T3-E1 osteoblastic cells. The analysis followed by validation by reverse transcription-polymerase chain reaction and immunochemical staining revealed that endoglin, which had been shown to associate with transforming growth factor (TGF)-b and bone morphogenetic proteins (BMPs) as signaling modulators, was abundantly expressed in PDL cells but absent in osteoblastic cells. The knockdown of endoglin greatly suppressed the BMP-2-induced osteoblastic differentiation of PDL cells and subsequent mineralization. Interestingly, the endoglin knockdown did not alter the level of Smad-1/5/8 phosphorylation induced by BMP-2, while it suppressed the BMP-2-induced expression of Id1, a representative BMP-responsive gene. Therefore, it is conceivable that endoglin regulates the expression of BMP-2-responsive genes in PDL cells at some site downstream of Smad-1/5/8 phosphorylation. Alternatively, wefound that Smad-2 aswell as Smad-1/5/8was phosphorylated by BMP-2 in the PDL cells, and that the BMP-2-induced Smad-2 phosphorylation was suppressed by the endoglin knockdown. These results, taken together, raise a possibility that PDL cells respond to BMP-2 via a unique signaling pathway dependent on endoglin, which is involved in the osteoblastic differentiation and mineralization of the cells.",
author = "Osamu Ishibashi and Mika Ikegame and Fumio Takizawa and Tatsuya Yoshizawa and Moksed, {Md Ali} and Futabako Iizawa and Hisashi Mera and Akio Matsuda and Hiroyuki Kawashima",
year = "2010",
month = "2",
doi = "10.1002/jcp.21968",
language = "English",
volume = "222",
pages = "465--473",
journal = "Journal of Cellular Physiology",
issn = "0021-9541",
publisher = "Wiley-Liss Inc.",
number = "2",

}

TY - JOUR

T1 - Endoglin is involved in BMP-2-induced osteogenic differentiation of periodontal ligament cells through a pathway independent of Smad-1/5/8 phosphorylation

AU - Ishibashi, Osamu

AU - Ikegame, Mika

AU - Takizawa, Fumio

AU - Yoshizawa, Tatsuya

AU - Moksed, Md Ali

AU - Iizawa, Futabako

AU - Mera, Hisashi

AU - Matsuda, Akio

AU - Kawashima, Hiroyuki

PY - 2010/2

Y1 - 2010/2

N2 - The periodontal ligament (PDL), a connective tissue located between the cementum of teeth and the alveolar bone of mandibula, plays a crucial role in the maintenance and regeneration of periodontal tissues. The PDL contains fibroblastic cells of a heterogeneous cell population, from which we have established several cell lines previously. To analyze characteristics unique for PDL at a molecular level, we performed cDNA microarray analysis of the PDL cells versus MC3T3-E1 osteoblastic cells. The analysis followed by validation by reverse transcription-polymerase chain reaction and immunochemical staining revealed that endoglin, which had been shown to associate with transforming growth factor (TGF)-b and bone morphogenetic proteins (BMPs) as signaling modulators, was abundantly expressed in PDL cells but absent in osteoblastic cells. The knockdown of endoglin greatly suppressed the BMP-2-induced osteoblastic differentiation of PDL cells and subsequent mineralization. Interestingly, the endoglin knockdown did not alter the level of Smad-1/5/8 phosphorylation induced by BMP-2, while it suppressed the BMP-2-induced expression of Id1, a representative BMP-responsive gene. Therefore, it is conceivable that endoglin regulates the expression of BMP-2-responsive genes in PDL cells at some site downstream of Smad-1/5/8 phosphorylation. Alternatively, wefound that Smad-2 aswell as Smad-1/5/8was phosphorylated by BMP-2 in the PDL cells, and that the BMP-2-induced Smad-2 phosphorylation was suppressed by the endoglin knockdown. These results, taken together, raise a possibility that PDL cells respond to BMP-2 via a unique signaling pathway dependent on endoglin, which is involved in the osteoblastic differentiation and mineralization of the cells.

AB - The periodontal ligament (PDL), a connective tissue located between the cementum of teeth and the alveolar bone of mandibula, plays a crucial role in the maintenance and regeneration of periodontal tissues. The PDL contains fibroblastic cells of a heterogeneous cell population, from which we have established several cell lines previously. To analyze characteristics unique for PDL at a molecular level, we performed cDNA microarray analysis of the PDL cells versus MC3T3-E1 osteoblastic cells. The analysis followed by validation by reverse transcription-polymerase chain reaction and immunochemical staining revealed that endoglin, which had been shown to associate with transforming growth factor (TGF)-b and bone morphogenetic proteins (BMPs) as signaling modulators, was abundantly expressed in PDL cells but absent in osteoblastic cells. The knockdown of endoglin greatly suppressed the BMP-2-induced osteoblastic differentiation of PDL cells and subsequent mineralization. Interestingly, the endoglin knockdown did not alter the level of Smad-1/5/8 phosphorylation induced by BMP-2, while it suppressed the BMP-2-induced expression of Id1, a representative BMP-responsive gene. Therefore, it is conceivable that endoglin regulates the expression of BMP-2-responsive genes in PDL cells at some site downstream of Smad-1/5/8 phosphorylation. Alternatively, wefound that Smad-2 aswell as Smad-1/5/8was phosphorylated by BMP-2 in the PDL cells, and that the BMP-2-induced Smad-2 phosphorylation was suppressed by the endoglin knockdown. These results, taken together, raise a possibility that PDL cells respond to BMP-2 via a unique signaling pathway dependent on endoglin, which is involved in the osteoblastic differentiation and mineralization of the cells.

UR - http://www.scopus.com/inward/record.url?scp=73349089657&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=73349089657&partnerID=8YFLogxK

U2 - 10.1002/jcp.21968

DO - 10.1002/jcp.21968

M3 - Article

VL - 222

SP - 465

EP - 473

JO - Journal of Cellular Physiology

JF - Journal of Cellular Physiology

SN - 0021-9541

IS - 2

ER -