A matter of origin - identification of SEMA3A, BGLAP, SPP1 and PHEX as distinctive molecular features between bone site-specific human osteoblasts on transcription level

Weiping Zhang; Sibylle Rau; Konstantinos Kotzagiorgis; René Rothweiler; Susanne Nahles; Eric Gottwald; Bernd Rolauffs; Thorsten Steinberg; Katja Nelson; Brigitte Altmann

doi:10.3389/fbioe.2022.918866

A matter of origin - identification of SEMA3A, BGLAP, SPP1 and PHEX as distinctive molecular features between bone site-specific human osteoblasts on transcription level

Front Bioeng Biotechnol. 2022 Sep 28:10:918866. doi: 10.3389/fbioe.2022.918866. eCollection 2022.

Authors

Affiliations

¹ G.E.R.N Research Center for Tissue Replacement, Regeneration & Neogenesis, Department of Oral- and Craniomaxillofacial Surgery, Medical Center, University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
² Department of Oral and Craniomaxillofacial Surgery, Medical Center, University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
³ G.E.R.N Research Center for Tissue Replacement, Regeneration & Neogenesis, Department of Prosthetic Dentistry, Medical Center, University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
⁴ Department of Oral and Maxillofacial Surgery, Berlin Institute of Health, Corporate Member of Freie Universität Berlin, Charité - Universitätsmedizin Berlin, Humboldt-Universität zu Berlin, Berlin, Germany.
⁵ Group 3D Cell Culture Systems, Institute of Functional Interfaces, Karlsruhe Institute of Technology, Karlsruhe, Germany.
⁶ G.E.R.N Research Center for Tissue Replacement, Regeneration & Neogenesis, Department of Orthopedics and Trauma Surgery, Medical Center, University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
⁷ Department of Oral Biotechnology, Center for Dental Medicine, Medical Center, University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.

Abstract

In oral and maxillofacial bone reconstruction, autografts from the iliac crest represent the gold standard due to their superior clinical performance, compared to autografts derived from other extraoral regions. Thus, the aim of our study was to identify putative differences between osteoblasts derived from alveolar (hOB-A) and iliac crest (hOB-IC) bone of the same donor (nine donors) by means of their molecular properties in 2D and 3D culture. We thereby focused on the gene expression of biomarkers involved in osteogenic differentiation, matrix formation and osteoclast modulation. Furthermore, we examined the transcriptional response to Vit.D3 in hOB-A and hOB-IC. Our results revealed different modulation modes of the biomarker expression in osteoblasts, namely cell origin/bone entity-dependent, and culture configuration- and/or time-dependent modulations. SEMA3A, SPP1, BGLAP and PHEX demonstrated the strongest dependence on cell origin. With respect to Vit.D3-effects, BGLAP, SPP1 and ALPL displayed the highest Vit.D3-responsiveness. In this context we demonstrated that the transcriptional Vit.D3-response concerning SPP1 and ALPL in human osteoblasts depended on the cell origin. The results indicate a higher bone remodeling activity of iliac crest than alveolar osteoblasts and support the growing evidence that a high osteoclast activity at the host-/donor bone interface may support graft integration.

Keywords: 3D-microchip culture; alveolar bone; bone grafts; gene expression analysis; iliac crest; in vitro model; osteoblasts; vitamin D.