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 journalArticlepeer-review

28 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

ASJC Scopus subject areas

  • Physiology
  • Clinical Biochemistry
  • Cell Biology

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