IADR Abstract Archives
Human Gingival Fibroblasts Rescue Osteoblasts Differentiation After Zoledronic Acid Administration
Objectives: Medication related osteonecrosis of the jaw (MRONJ) is a severe complication which affects 8% of oncologic patients receiving Zoledronic acid (ZOL). MRONJ manifests as exposed bone in the maxillofacial region. The pathophysiology is not well understood, and severe cases require extensive surgery. ZOL, a nitrogen containing bisphosphonate, inhibits osteoclasts differentiation and function. However, ZOL's influence on the interaction between osteoblasts and soft tissue has not been thoroughly investigated.
Aim: Investigate ZOL influence on the interaction between soft tissue and osteoblasts
Methods: Human gingival fibroblasts and keratinocytes were cultured with 5μM ZOL solution for 24 hours and the conditioned medium (CM) was collected. To evaluate the effect of soft tissue cells on osteoblasts' viability and proliferation, the CM was added to the culture medium of U2OS and XTT assay was performed. Additionally, MSCs and U2OS were cultured in osteogenic differentiation medium with ZOL or soft tissue CM. Their influence was evaluated using ALP and Alizarin Red staining.
Results: Proliferation and viability of the control group increased while the cells in groups incubated with ZOL and CM of keratinocytes treated with ZOL abolished after 48h . The osteogenic differentiation of U2OS was reduced by 70% and 50% by ZOL and CM of keratinocytes, respectively (compared to 100% in osteogenic medium). However, CM of fibroblasts which were cultured with ZOL protected U2OS and MSCs from the cytotoxic effect of ZOL: the osteogenic differentiation of the cells was completed with only a slight reduction in cell viability.
Conclusions: ZOL reduces viability, proliferation and differentiation of U2OS. CM of fibroblasts which were treated with ZOL rescued U2OS proliferation and differentiation. These results suggest that fibroblasts secrete factors which can neutralize ZOL toxicity. This finding may help develop new strategies to prevent or treat MRONJ.
Aim: Investigate ZOL influence on the interaction between soft tissue and osteoblasts
Methods: Human gingival fibroblasts and keratinocytes were cultured with 5μM ZOL solution for 24 hours and the conditioned medium (CM) was collected. To evaluate the effect of soft tissue cells on osteoblasts' viability and proliferation, the CM was added to the culture medium of U2OS and XTT assay was performed. Additionally, MSCs and U2OS were cultured in osteogenic differentiation medium with ZOL or soft tissue CM. Their influence was evaluated using ALP and Alizarin Red staining.
Results: Proliferation and viability of the control group increased while the cells in groups incubated with ZOL and CM of keratinocytes treated with ZOL abolished after 48h . The osteogenic differentiation of U2OS was reduced by 70% and 50% by ZOL and CM of keratinocytes, respectively (compared to 100% in osteogenic medium). However, CM of fibroblasts which were cultured with ZOL protected U2OS and MSCs from the cytotoxic effect of ZOL: the osteogenic differentiation of the cells was completed with only a slight reduction in cell viability.
Conclusions: ZOL reduces viability, proliferation and differentiation of U2OS. CM of fibroblasts which were treated with ZOL rescued U2OS proliferation and differentiation. These results suggest that fibroblasts secrete factors which can neutralize ZOL toxicity. This finding may help develop new strategies to prevent or treat MRONJ.