Article

Signaling responses of osteoblast cells to hydroxyapatite: the activation of ERK and SOX9.

School of Materials Science and Engineering, Seoul National University, Seoul, Korea.
Journal of Bone and Mineral Metabolism (Impact Factor: 2.22). 02/2008; 26(2):138-42. DOI: 10.1007/s00774-007-0804-6
Source: PubMed

ABSTRACT The intracellular signaling cascade triggered as a result of the surface chemistry of the bone mineral hydroxyapatite (HA) remains largely unknown. In this study, we found that the ERK signaling molecule is activated in response to HA. Moreover, we have performed the first systemic analysis of expression profiles using microarray technology. Eleven genes, including those involved in calcium regulation and bone matrix formation, showed a greater than 2.0-fold change in expression level in response to HA. Among those genes upregulated by HA was the gene encoding SOX9, whose expression we confirmed by real-time PCR analysis with a 5.7-fold increase in expression. Taken together, our results suggest that the activation of ERK and SOX9 by HA could have important implications for understanding the mechanisms by which cells respond on a molecular level to HA.

0 Bookmarks
 · 
105 Views
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Osteoporosis is a complex human disease that results in increased susceptibility to fragility fractures. It can be phenotypically characterized using several traits, including bone mineral density, bone size, bone strength, and bone turnover markers. The identification of gene variants that contribute to osteoporosis phenotypes, or responses to therapy, can eventually help individualize the prognosis, treatment, and prevention of fractures and their adverse outcomes. Our previously published reviews have comprehensively summarized the progress of molecular genetic studies of gene identification for osteoporosis and have covered the data available to the end of September 2007. This review represents our continuing efforts to summarize the important and representative findings published between October 2007 and November 2009. The topics covered include genetic association and linkage studies in humans, transgenic and knockout mouse models, as well as gene-expression microarray and proteomics studies. Major results are tabulated for comparison and ease of reference. Comments are made on the notable findings and representative studies for their potential influence and implications on our present understanding of the genetics of osteoporosis.
    Endocrine reviews 03/2010; 31(4):447-505. · 19.76 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Formation of the native bone extracellular matrix (ECM) provides an attractive template for bone tissue engineering. The structural support and biological complexity of bone ECM are provided within a composite microenvironment that consists of an organic fibrous network reinforced by inorganic hydroxyapatite (HA) nanoparticles. Recreating this biphasic assembly, a bone ECM analogous scaffold comprising self-assembling peptide amphiphile (PA) nanofibers and interspersed HA nanoparticles was investigated. PAs were endowed with biomolecular ligand signaling using a synthetically inscribed peptide sequence (i.e., RGDS) and integrated with HA nanoparticles to form a biphasic nanomatrix hydrogel. It was hypothesized the biphasic hydrogel would induce osteogenic differentiation of human mesenchymal stem cells (hMSCs) and improve bone healing as mediated by RGDS ligand signaling within PA nanofibers and embedded HA mineralization source. Viscoelastic stability of the biphasic PA hydrogels was evaluated with different weight concentrations of HA for improved gelation. After demonstrating initial viability, long-term cellularity and osteoinduction of encapsulated hMSCs in different PA hydrogels were studied in vitro. Temporal progression of osteogenic maturation was assessed by gene expression of key markers. A preliminary animal study demonstrated bone healing capacity of the biphasic PA nanomatrix under physiological conditions using a critical size femoral defect rat model. The combination of RGDS ligand signaling and HA nanoparticles within the biphasic PA nanomatrix hydrogel demonstrated the most effective osteoinduction and comparative bone healing response. Therefore, the biphasic PA nanomatrix establishes a well-organized scaffold with increased similarity to natural bone ECM with the prospect for improved bone tissue regeneration.
    ACS Nano 11/2011; 5(12):9463-79. · 12.03 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Glycogen synthase kinase 3 beta (GSK-3β) is an essential negative regulator or "brake" on many anabolic-signalling pathways including Wnt and insulin. Global deletion of GSK-3β results in perinatal lethality and various skeletal defects. The goal of our research was to determine GSK-3β cell-autonomous effects and postnatal roles in the skeleton. We used the 3.6Kb Col1a1 promoter to inactivate the Gsk3b gene (Col1a1-Gsk3b KO) in skeletal cells. Mutant mice exhibit decreased body fat and postnatal bone growth, as well as delayed development of several skeletal elements. Surprisingly, the mutant mice display decreased circulating glucose and insulin levels despite normal expression of GSK-3β in metabolic tissues. We showed that these effects are due to an increase in global insulin sensitivity. Most of the male mutant mice died post weaning. Prior to death, blood glucose changed from low to high, suggesting a possible switch from insulin sensitivity to resistance. These male mice die with extremely large bladders that are preceded by damage to the urogenital tract, defects that are also seen type II diabetes. Our data suggests that skeletal-specific deletion of GSK-3β affects global metabolism and sensitizes male mice to developing type II diabetes.
    Endocrinology 07/2013; · 4.72 Impact Factor

Full-text (2 Sources)

View
47 Downloads
Available from
Jun 2, 2014