Alterations of bone proteins in medication-related osteonecrosis of the jaw.

Changes in the protein expression pattern of osteoblastic lineage cells from the alveolar bone (OLAB) during medication-related osteonecrosis of the jaw (MRONJ) have rarely been investigated. This lack of information is partly because of the limited availability of healthy samples and the lack of human alveolar bone cell lines for research. The aim of the present study was to investigate the bone proteins collagen 1, runt-related transcription factor 2 (RUNX2), and tumor necrosis factor ligand superfamily member 11 (RANKL). Furthermore, we established a cell lineage of OLAB suitable for the analyses of protein expression. We used immunohistochemistry to determine protein expression patterns in vivo. OLAB were treated during culture with zoledronate or denosumab and analyzed by immunocytochemistry and western blotting. Collagen 1 was decreased in vivo in patients with MRONJ and in vitro by denosumab. Zoledronate reduced the level of RUNX2 in vitro. However, RANKL was not significantly affected by zoledronate or denosumab. The results of the present study will help us elucidate the cellular mechanisms of MRONJ. Although culture of OLAB with zoledronate and denosumab significantly altered the protein expression patterns, future research is needed to examine the effects of bone scaffolds, biofilms, and additional cell types mimicking in vivo conditions.