Abstract
Therapeutic effects of zoledronic acid (ZOL) on giant cell tumour of bone (GCT) have been proven. Apoptosis induction was considered to be one of the mechanisms of ZOL tumour inhibition. In this study, we presented the possibility of an osteogenic differentiation stimulation mechanism of ZOL and further investigated dosage and time effects. We treated stromal cells of GCT (GCTSC) with ZOL for 48 hours at different concentrations (0 μM, 0.01 μM, 0.1 μM, 1 μM, 5 μM, 30 μM) and assessed apoptotic and osteogenic differentiation markers with immunohistochemical techniques and real-time quantitative RT-PCR. Our results suggested that ZOL enhanced mRNA expression of Cbfa-1, osterix and osteocalcin genes with a maximum effect at 1 μM in GCTSC. Time course experiments indicated a time dependent osteogenic differentiation effect. In conclusion, ZOL may be considered as an adjuvant in the treatment of GCT not only by inducing apoptosis but also by stimulating osteogenic differentiation of remaining tumor stromal cells after surgery.
Highlights
Giant cell tumor of bone (GCT) is a common benign tumor that comprises 5%-20% of primary bone tumors in adults (Turcotte, 2006)
Our results suggested that zoledronic acid (ZOL) enhanced mRNA expression of Cbfa-1, osterix and osteocalcin genes with a maximum effect at 1μM in GCTSC
ZOL may be considered as an adjuvant in the treatment of GCT by inducing apoptosis and by stimulating osteogenic differentiation of remaining tumor stromal cells after surgery
Summary
Giant cell tumor of bone (GCT) is a common benign tumor that comprises 5%-20% of primary bone tumors in adults (Turcotte, 2006). Stromal cell (GCTSC) is thought to be the primary neoplastic cells owing to their abilities of stable proliferation in culture and tumor formation in mice (Cowan and Singh, 2013). It expresses differentiation features of mesenchymal lineage and pre-osteoblast phenotype (Werner, 2006). Many adjuvant treatments including physical methods (blurring, hypothermic or hyperthermic reagents), chemical methods (phenol, hydrogen peroxide) and biologic modalities (bisphosphonates, interferon, denosumab) have been suggested to eliminate microscopic lesions of the disease after surgery so as to reduce the recurrence rate (Gibbs et al, 2005).
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