Effects of Osteogenic Protein-1 (OP-1, BMP-7) on Gene Expression in Cultured Medial Collateral Ligament Cells

Alicia D. Tsai, Lee Chuan C. Yeh, John C. Lee

Research output: Contribution to journalArticle

23 Scopus citations

Abstract

Osteogenic protein-1 (OP-1, also called BMP-7), a member of the BMP family and the TGF-β superfamily, induces formation of new bone and cartilage, but also regulates a wide array of processes. In the present study, the expression of several characteristic biochemical markers of ligaments, such as Sixl, Scleraxis, aggrecan, and type I collagen in primary cultures of adult rat medial collateral ligament(MCL) cells was determined. The effects of OP-1 on cell proliferation and on gene expression were subsequently examined. OP-1 stimulated cell proliferation, alkaline phosphatase (AP) activity, and the steady-state mRNA levels of the transcription factor Runx2/Cbfal in a dose- and time-dependent manner. The mRNA levels of type I collagen only increased slightly, but the activity of the cloned collagen promoter increased by 2-fold in transiently transfected MCL cells. OP-1 also stimulated aggrecan mRNA expression. The mRNA levels of Sixl and Scleraxis were not detectably altered by OP-1. In control cultures, the steady-state mRNA levels of ActR-I, BMPR-IA, BMPR-IB, and BMPR-II increased as a function of time in culture. The mRNA levels of BMP-1 and -4 increased significantly after 12 days, but those of BMP-2 and -6 did not change The GDF-1, -3, -5, -6, and -8 mRNA levels in the control cultures also increased as a function of time. OP-1 treatment stimulated mRNA expression of BMPR-IA and BMPR-II, but had little effect on ActR-I and BMPR-IB mRNA expression. OP-1 lowered the BMP-1, -2, and -6 mRNA levels without changing the BMP-4 mRNA level. OP-1 treatment also reduced the mRNA levels of GDFs detected. In summary, the present study demonstrated that OP-1 stimulated cell proliferation and mRNA expression of several biochemical markers in this ligament cell culture model and established the spatial and temporal appearance of several members of the TGF-β superfamily.

Original languageEnglish (US)
Pages (from-to)777-791
Number of pages15
JournalJournal of Cellular Biochemistry
Volume90
Issue number4
DOIs
Publication statusPublished - Nov 1 2003

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Keywords

  • BMP
  • BMP receptors
  • Gene expression
  • Ligament
  • MCL
  • OP-1
  • Runx2/Cbfal
  • Scleraxis
  • Sixl

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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