Characterization of the osteogenic and osteoclastogenic biomarker expression in site-specific osteoblasts derived from the same donor in a 3D-microchip-device: A contribution to the identification of candidate markers of the bone transplant competence

• Applicant: Privatdozentin Dr. Brigitte Altmann, Ph.D.
• Subject Area: Dentistry, Oral Surgery
• Term: from 2017 to 2020
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 397303329

In oral and maxillofacial bone reconstruction of large size defects autologous bone grafts from iliac crest still represent the gold standard due to their superior clinical performance when compared to autografts derived from other anatomic regions like the mandibular bone. As a possible cause for this, putative site-specific variations between bone tissue derived from the hip and jaw are discussed. Previous in vitro studies demonstrate functional cellular differences between osteoblasts from the alveolar bone and the iliac crest of the same donor. Preliminary results corroborate the molecular and phenotypic heterogeneity of bone cells and thus of bone tissue, but further investigations are still needed to identify the biomolecules responsible for the superior clinical performance of iliac bone grafts. Therefore, the aim of the proposed project is to identify putative differences between human osteoblasts derived from alveolar bone and iliac crest of the same donor by means of their molecular properties in a microchip-based 3D cell culture system. This system allows more in-vivo-relevant results with respect to bone-site-specific cell behaviour with emphasize on the osteogenic differentiation of primary human osteoblasts. Morphogenesis, formation of bone-specific extracellular matrix and tissue-specific biomarker expression of osteoblasts during the osteogenic differentiation towards osteocytes will be analysed by scanning electron microscopy, histological and immunohistochemical staining of resin-embedded sections and by gene expression analysis. In an additional approach we will then further analyse the expression of osteoclast modulating signalling molecules in osteoblasts and osteocytes or osteocyte-like cells on gene and protein expression level. This strategy enables us to identify possible differences between bone cells derived from alveolar bone and iliac crest with respect to their osteogenic and osteoclastogenic potential on molecular level. The results of this study will provide new insights into the molecular basics associated with site-specific properties of bone tissue, and thus will also contribute to a biological-clinical orientation of innovative biomaterial-based therapeutic approaches in the field of oral bone augmentation surgery.

• DFG Programme: Research Grants
• Co-Investigator: Professorin Dr. Katja Nelson