Bone Morphogenetic Protein 2 Induces Dental Follicle Cells to Differentiate Toward a Cementoblast/Osteoblast Phenotype

Authors

  • Ming Zhao,

    1. Department of Periodontics/Prevention/Geriatrics, School of Dentistry, University of Michigan, Ann Arbor, Michigan, USA
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  • Guozhi Xiao,

    1. Department of Periodontics/Prevention/Geriatrics, School of Dentistry, University of Michigan, Ann Arbor, Michigan, USA
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  • Janice E. Berry,

    1. Department of Periodontics/Prevention/Geriatrics, School of Dentistry, University of Michigan, Ann Arbor, Michigan, USA
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  • Renny T. Franceschi,

    1. Department of Periodontics/Prevention/Geriatrics, School of Dentistry, University of Michigan, Ann Arbor, Michigan, USA
    2. Department of Biological Chemistry, University of Michigan, Ann Arbor, Michigan, USA
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  • Anand Reddi,

    1. Department of Periodontics/Prevention/Geriatrics, School of Dentistry, University of Michigan, Ann Arbor, Michigan, USA
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  • Martha J. Somerman D.D.S., Ph.D.

    Corresponding author
    1. Department of Periodontics/Prevention/Geriatrics, School of Dentistry, University of Michigan, Ann Arbor, Michigan, USA
    2. Department of Pharmacology, School of Medicine, University of Michigan, Ann Arbor, Michigan, USA
    • Department of Periodontics/Prevention/Geriatrics, University of Michigan, School of Dentistry, 1011 North University Avenue, Ann Arbor, MI 48109-1078, USA
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  • The authors have no conflict of interest.

Abstract

When triggered appropriately, dental follicle cells are considered to be able to differentiate toward a cementoblast/osteoblast phenotype. However, factors and mechanisms regulating follicle cell differentiation remain undefined. This study focused on determining the ability of bone morphogenetic protein (BMP) 2 to promote the differentiation of follicle cells and periodontal ligament (PDL) cells along a cementoblast/osteoblast pathway. Follicle cells and PDL cells were isolated from the first molar region of CD-1 mice and immortalized with SV40. Both cell types expressed BMP-4 and BMP receptors (BMPR) IA and II, but only follicle cells expressed BMP-2 mRNA. Cells were exposed to recombinant human BMP (rhBMP)-2 (0–100 ng/ml) and Northern blots were used to determine the expression of mineral-associated markers. BMP-2, in a dose- and time-dependent manner, induced cementoblast/osteoblast differentiation of follicle cells, as reflected by enhanced core binding factor α1 (Cbfa1), bone sialoprotein (BSP), and osteocalcin (OCN) mRNA expression and enhanced mineral formation. U0126, a specific inhibitor of MEK-1/2 members of the MAPK family, abolished BMP-2-mediated expression of BSP and OCN. In contrast, exposure of PDL cells to BMP-2 resulted in modest expression of OCN and minimal promotion of mineralization. These results suggest that BMP-2 triggers follicle cells to differentiate toward a cementoblast/osteoblast phenotype and that the MAPK pathway is involved.

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