The Distinct Roles of Growth/Differentiation Factor-5 in Cell Proliferation and Odontoblast Differentiation from Dental Pulp Cells

Growth/differentiation factor-5 (GDF-5) belongs to the bone morphogenetic protein (BMP) family, which is expressed in dental pulp tissues. To date, various studies have reported that BMP-family growth factors can induce cells isolated from dental pulp tissues to differentiate into odontoblasts. Nevertheless, the effect of GDF-5 on odontoblast differentiation from dental pulp tissues remains unknown. In this study, we assayed the effect of exogenous mouse recombinant GDF-5 on cell proliferation of dental pulp cells and determined the expression levels of odontoblast differentiation marker genes in the cells of isolated mouse dental pulp tissues in the presence of GDF-5. There were no significant differences in dental pulp cell proliferation patterns related to the absence or presence of GDF-5 after seven days of culture. Odontoblast marker gene levels, on the other hand, were significantly elevated after seven days of culture in the presence of GDF-5. GDF-5 also increased the gene expression and enzyme activity of alkaline phosphatase. Furthermore, dental pulp cells cultured in the presence of GDF-5 formed alizarin redpositive nodules after 10 days of culture. These results indicate that, although GDF-5 may have no effect on cell proliferation in isolated dental pulp tissue, it could promote odontoblast differentiation.

[1]  池田 秀吉 Engineering Bone Formation from Human Dental Pulp- and Periodontal Ligament-Derived Cells , 2011 .

[2]  J. Jeng,et al.  Transforming growth factor 1 down-regulates Runx-2 and alkaline phosphatase activity of human dental pulp cells via ALK 5 / Smad 2 / 3 signaling , 2011 .

[3]  S. Harris,et al.  Immortalized mouse floxed Bmp2 dental papilla mesenchymal cell lines preserve odontoblastic phenotype and respond to BMP2 , 2010, Journal of cellular physiology.

[4]  I. Asahina,et al.  Differential effects of growth differentiation factor-5 on porcine dental papilla- and follicle-derived cells , 2010, Growth factors.

[5]  T. Inai,et al.  Growth Differentiation Factor 5 (GDF-5) Induces Matrix Metalloproteinase 2 (MMP-2) Expression in Periodontal Ligament Cells and Modulates MMP-2 and MMP-13 Activity in Osteoblasts: , 2010 .

[6]  J. Jansen,et al.  Mineralized Tissue Formation by BMP2-transfected Pulp Stem Cells , 2009, Journal of dental research.

[7]  Nian-hua Zhang,et al.  Adenovirus-mediated recombinant human bone morphogenetic protein-7 expression promotes differentiation of human dental pulp cells. , 2007, Journal of endodontics.

[8]  Y. Izumi,et al.  Recombinant human growth/differentiation factor-5 (rhGDF-5) induced bone formation in murine calvariae. , 2006, Journal of periodontal research.

[9]  A. Akamine,et al.  The application of tissue engineering to regeneration of pulp and dentin in endodontics. , 2005, Journal of endodontics.

[10]  Phil G. Campbell,et al.  Phosphophoryn Regulates the Gene Expression and Differentiation of NIH3T3, MC3T3-E1, and Human Mesenchymal Stem Cells via the Integrin/MAPK Signaling Pathway* , 2004, Journal of Biological Chemistry.

[11]  R. Tuan,et al.  Distinct functions of BMP4 and GDF5 in the regulation of chondrogenesis , 2004, Journal of cellular biochemistry.

[12]  K. Bessho,et al.  Acceleration effect of human recombinant bone morphogenetic protein-2 on differentiation of human pulp cells into odontoblasts. , 2004, Journal of endodontics.

[13]  Y. Izumi,et al.  Effects of growth/differentiation factor-5 on human periodontal ligament cells. , 2003, Journal of periodontal research.

[14]  I. Ishikawa,et al.  Gene Expression of Growth Differentiation Factors in the Developing Periodontium of Rat Molars , 2003, Journal of dental research.

[15]  R. Terkeltaub,et al.  Tissue-nonspecific alkaline phosphatase and plasma cell membrane glycoprotein-1 are central antagonistic regulators of bone mineralization , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[16]  Hideki Yoshikawa,et al.  Bone Morphogenetic Protein Signals Are Required for Cartilage Formation and Differently Regulate Joint Development During Skeletogenesis , 2002, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[17]  K. Miyazono,et al.  Synergistic effects of different bone morphogenetic protein type I receptors on alkaline phosphatase induction. , 2001, Journal of cell science.

[18]  F. Luyten,et al.  Mechanisms of GDF-5 action during skeletal development. , 1999, Development.

[19]  A. Akamine,et al.  Transforming growth factor-β superfamily members expressed in rat incisor pulp , 1998 .

[20]  I. Ishikawa,et al.  Gene expression of growth and differentiation factors-5, -6, and -7 in developing bovine tooth at the root forming stage. , 1998, Biochemical and biophysical research communications.

[21]  T. Kawamoto,et al.  Differential effects of various growth factors and cytokines on the syntheses of DNA, type I collagen, laminin, fibronectin, osteonectin/secreted protein, acidic and rich in cysteine (SPARC), and alkaline phosphatase by human pulp cells in culture , 1998, Journal of cellular physiology.

[22]  A. Akamine,et al.  Transforming growth factor-beta superfamily members expressed in rat incisor pulp. , 1998, Archives of oral biology.

[23]  S. Kuhara,et al.  Expression of TGF-β Superfamily Receptors in Dental Pulp , 1997 .

[24]  S. Kuhara,et al.  Temporal changes in expression of transforming growth factor-beta superfamily members and their receptors during bovine preodontoblast differentiation in vitro. , 1997, Archives of oral biology.

[25]  S. Kuhara,et al.  Expression of TGF-beta superfamily receptors in dental pulp. , 1997, Journal of dental research.

[26]  R. H. Smoke,et al.  Expression of genes for bone morphogenetic proteins and receptors in human dental pulp. , 1996, Archives of oral biology.

[27]  K. Miyazono,et al.  Identification of Type I and Type II Serine/Threonine Kinase Receptors for Growth/Differentiation Factor-5* , 1996, The Journal of Biological Chemistry.

[28]  W. Butler,et al.  The nature and functional significance of dentin extracellular matrix proteins. , 1995, The International journal of developmental biology.

[29]  N. Copeland,et al.  Limb alterations in brachypodism mice due to mutations in a new member of the TGFβ-superfamily , 1994, Nature.

[30]  I. Asahina,et al.  Human osteogenic protein-1 induces both chondroblastic and osteoblastic differentiation of osteoprogenitor cells derived from newborn rat calvaria , 1993, The Journal of cell biology.

[31]  V. Rosen,et al.  Recombinant human bone morphogenetic protein-2 stimulates osteoblastic maturation and inhibits myogenic differentiation in vitro , 1991, The Journal of cell biology.