Limits...
Modifying the osteoblastic niche with zoledronic acid in vivo-potential implications for breast cancer bone metastasis.

Haider MT, Holen I, Dear TN, Hunter K, Brown HK - Bone (2014)

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.

View Article: PubMed Central - PubMed

Affiliation: CR-UK/YCR Cancer Research Centre, University of Sheffield, Sheffield, UK. Electronic address: mhaider1@sheffield.ac.uk.

Show MeSH

Related in: MedlinePlus

Confirmation of ZOL-effects on GFP-expressing osteoblastic cells in a genetically engineered mouse model.(A) Reduction of GFP signal in tibia, femur, ribcages and rib sections of a ZOL treated mouse compared to control. Arrows indicate the osteoblast rich growth plate area. (B) The reduction in osteoblasts on trabeculi can also be seen by GFP-immunohistochemistry on paraffin sections of the tibia of 6-week old mice. Osteoblastic cells are stained brown, scale bar = 500 μm. Quantification of osteoblasts by morphology or after GFP-immunohostochemistry in (C) 6-week old mice (n = 2/group) and (D) 9–10-week old animals (n = 2/group) 5 days after a single injection of ZOL (100 μg/kg, i.p) or PBS. Bottom panel (E) shows toluidine blue staining of proteoglycan in bone, scale bar = 300 μm.
© Copyright Policy - CC BY-NC-SA
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4127787&req=5

f0025: Confirmation of ZOL-effects on GFP-expressing osteoblastic cells in a genetically engineered mouse model.(A) Reduction of GFP signal in tibia, femur, ribcages and rib sections of a ZOL treated mouse compared to control. Arrows indicate the osteoblast rich growth plate area. (B) The reduction in osteoblasts on trabeculi can also be seen by GFP-immunohistochemistry on paraffin sections of the tibia of 6-week old mice. Osteoblastic cells are stained brown, scale bar = 500 μm. Quantification of osteoblasts by morphology or after GFP-immunohostochemistry in (C) 6-week old mice (n = 2/group) and (D) 9–10-week old animals (n = 2/group) 5 days after a single injection of ZOL (100 μg/kg, i.p) or PBS. Bottom panel (E) shows toluidine blue staining of proteoglycan in bone, scale bar = 300 μm.

Mentions: For the quantification of osteoblasts, we identified the cells by assessing their specific morphology as previously described [11]. 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.


Modifying the osteoblastic niche with zoledronic acid in vivo-potential implications for breast cancer bone metastasis.

Haider MT, Holen I, Dear TN, Hunter K, Brown HK - Bone (2014)

Confirmation of ZOL-effects on GFP-expressing osteoblastic cells in a genetically engineered mouse model.(A) Reduction of GFP signal in tibia, femur, ribcages and rib sections of a ZOL treated mouse compared to control. Arrows indicate the osteoblast rich growth plate area. (B) The reduction in osteoblasts on trabeculi can also be seen by GFP-immunohistochemistry on paraffin sections of the tibia of 6-week old mice. Osteoblastic cells are stained brown, scale bar = 500 μm. Quantification of osteoblasts by morphology or after GFP-immunohostochemistry in (C) 6-week old mice (n = 2/group) and (D) 9–10-week old animals (n = 2/group) 5 days after a single injection of ZOL (100 μg/kg, i.p) or PBS. Bottom panel (E) shows toluidine blue staining of proteoglycan in bone, scale bar = 300 μm.
© Copyright Policy - CC BY-NC-SA
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4127787&req=5

f0025: Confirmation of ZOL-effects on GFP-expressing osteoblastic cells in a genetically engineered mouse model.(A) Reduction of GFP signal in tibia, femur, ribcages and rib sections of a ZOL treated mouse compared to control. Arrows indicate the osteoblast rich growth plate area. (B) The reduction in osteoblasts on trabeculi can also be seen by GFP-immunohistochemistry on paraffin sections of the tibia of 6-week old mice. Osteoblastic cells are stained brown, scale bar = 500 μm. Quantification of osteoblasts by morphology or after GFP-immunohostochemistry in (C) 6-week old mice (n = 2/group) and (D) 9–10-week old animals (n = 2/group) 5 days after a single injection of ZOL (100 μg/kg, i.p) or PBS. Bottom panel (E) shows toluidine blue staining of proteoglycan in bone, scale bar = 300 μm.
Mentions: For the quantification of osteoblasts, we identified the cells by assessing their specific morphology as previously described [11]. 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.

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.

View Article: PubMed Central - PubMed

Affiliation: CR-UK/YCR Cancer Research Centre, University of Sheffield, Sheffield, UK. Electronic address: mhaider1@sheffield.ac.uk.

Show MeSH
Related in: MedlinePlus