Bevacizumab and Sunitinib Mediate Osteogenic and Pro-inflammatory Molecular Changes in Primary Human Alveolar Osteoblasts in Vitro

Overview

Journal Odontology

Specialty Dentistry

Date 2022 Feb 16

PMID 35171372

Authors

Elena Hofmann

Benedikt Eggers

Nils Heim

Franz-Josef Kramer

Marjan Nokhbehsaim

Werner Gotz

Affiliations

Soon will be listed here.

Abstract

Antiangiogenic medications target the de novo blood vessel formation in tumorigenesis. However, these novel drugs have been linked to the onset of medication-related osteonecrosis of the jaw (MRONJ). The aim of this in vitro study was to examine the effects of the vascular endothelial growth factor A (VEGFA) antibody bevacizumab (BEV) and the receptor tyrosine kinase inhibitor (RTKI) sunitinib (SUN) on primary human osteoblasts derived from the alveolar bone. Primary human alveolar osteoblasts (HAOBs) were treated with BEV or SUN for 48 h. Cellular metabolic activity was examined by XTT assay. Differentially regulated genes were identified by screening of 22 selected osteogenic and angiogenic markers by quantitative real-time reverse transcriptase polymerase chain reaction (qRT-PCR). Protein levels of alkaline phosphatase (ALP), collagen type 1, α1 (COL1A1) and secreted protein acidic and cysteine rich (SPARC) were examined by enzyme-linked immunoassay (ELISA). Treatment with BEV and SUN did not exhibit direct cytotoxic effects in HAOBs as confirmed by XTT assay. Of the 22 genes examined by qRT-PCR, four genes were significantly regulated after BEV treatment and eight genes in the SUN group as compared to the control group. Gene expression levels of ALPL, COL1A1 and SPARC were significantly downregulated by both drugs. Further analysis by ELISA indicated the downregulation of protein levels of ALP, COL1A1 and SPARC in the BEV and SUN groups. The effects of BEV and SUN in HAOBs may be mediated by alterations to osteogenic and catabolic markers. Therapeutic or preventive strategies in MRONJ may address drug-induced depression of osteoblast differentiation.

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