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Fig. 1.
RT-PCR for the osteoclastogenesis related cytokine mRNA from PBMCs of 12 patients with RA with low BMD and 12 age-matched normal individuals· The expression of osteoclastogenesis related cytokine mRNA was not different between the PBMCs of 12 patients with RA with low BMD and 12 age-matched normal individuals· The amount of the cytokine expression varied too much between individuals to compare each other in each group· The PCR condition was initial 10 minutes at 95oC, 35 cycles at 95oC for 30 seconds and 56oC for 60 seconds, and last 10 minutes at 72oC·
Fig. 2.
After culture the osteoclast from a patient with the RA (X200, light microscope, Counter stain with the Hematoxylin). TRAP positive giant cells with more than 3 nuclei were regarded as osteoclast. TRAP positive giant cells were generated from the human PBMCs after 3 weeks of culture (X400).
Fig. 3.
The number of the TRAP+ giant cell formation from PBMCs of 12 patients with RA with low BMD and 12 age-matched control individuals. They were not different between the groups (p= 0.117). Cell counts are per each well in 96-well culture plate expressed as mean±SD of triplicate culture.
Fig. 4.
Resorption pits were examined under magnifying glass and the percentage surface area of lacunar resorption on each dentine slice was determined as manufacturer's guide. Grade 0: 0%, Grade 1: 20%, Grade 2: 40%, Grade 3: 60%, Grade 4: 80%, Grade 5: 100% (X10).
Fig. 5.
The effect of the 18 hours alendronate pulse on the subsequent expression of the osteoclastogenesis related cytokines in a normal control· The increased IFN- γ expression and decreased RANK and IL-10 expression is noted·
Fig. 6.
(A) The culture of the whole PBMCs for 3 weeks showed many TRAP (+) giant cells (X400). (B) The pre-incubation of the whole PBMCs with the alendronate (100 M) for 24 hours before plating on the culture plate inhibited the development of the TRAP (+) giant cells almost completely (X400).
Fig. 7.
(A) The culture of the whole PBMCs on the OAAS™ plate for 4 weeks showed the many resorption pits, Grade 2 (X100). (B) The pre-incubation of the whole PBMCs with the alendronate (100 M) for 24 hours before plating on the OAAS™ plate inhibited the development of the resorption pits almost completely (X100).
Table 1.
Response of osteoclastogenesis related gene expression in PBMCs after 24 hours of alendronate (100 microM) incubation· The real time RT-PCR showed that the mRNA expression of the M-CSF, RANKL, TNF- α, IL-6, and IFN- γ increased· Among them the increase of IFN- γ was most prominent· But those of the RANK, TRAP, and cathepsin K decreased after alendronate pulse of the PBMCs· The IL-1 expression did not changed significantly· The Results of Real Time RT-PCR by “2-zMCT Method”
Table 2.
The count of the TRAP positive cells in 96 well culture plates before and after alendronate pulse· They were not different between the groups (p= 0·117)· The decrease of the TRAP (+) giant cells after alendronate pulse was almost com- plete· The developments of the TRAP (+) giant cells were inhibited markedly after alendronate pulse, but less markedly in RA
| Alendronate dose | RA (n=6) | Age matched control (n=6) | Young normal (n=6) |
|---|---|---|---|
| 0 μM | 23.9±9.41 | 22.8±6.31 | 18.2±7.73 |
| 100 μM | 7.1±4.12 | 0.5±0.84 | 0 |
| 200 μM | 1.8±0.75 | 0 | 0 |
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