Modifying the osteoblastic niche with zoledronic acid in vivo-potential implications for breast cancer bone metastasis.
Bottom Line: The associated cancer-induced bone disease is treated with bone-sparing agents like zoledronic acid.The effects on growth plate cartilage were visualised by toluidine blue staining.The number of circulating tumour cells was reduced in ZOL treated animals.
Affiliation: CR-UK/YCR Cancer Research Centre, University of Sheffield, Sheffield, UK. Electronic address: firstname.lastname@example.org.Show MeSH
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Mentions: For the quantification of osteoblasts, we identified the cells by assessing their specific morphology as previously described . In addition, we used a model system where mice have been genetically engineered to express GFP in cells of the osteoblastic lineage, facilitating identification and visualisation of these cells. In these animals, the inhibitory effect of ZOL on osteoblastic cells was evident in tissues and histological sections (Fig. 5A) when compared to control. GFP staining visualised that ZOL treatment predominantly altered osteoblastic cells/mm bone surface in the trabecular bone area while the cell density around the growth plate and the cortical bone was unaffected (Fig. 5B). Toluidine blue staining showed that zoledronic acid appeared to increase the amount of proteoglycan rich matrix in the metaphysis, and this stretched deeper into the extending front of the growth plate compared to control mice (Fig. 5E). The ZOL-induced increase in bone volume may therefore be a result of elevated endochondral ossification, as this excess matrix is normally resorbed by osteoclasts.
Affiliation: CR-UK/YCR Cancer Research Centre, University of Sheffield, Sheffield, UK. Electronic address: email@example.com.