External factors
| Category: |
Chemical compounds |
| Phenotype: |
Bisphosphonate-related osteonecrosis of the jaw |
| Experiment: |
MTT assay//Flow cytometry//SA-β-gal activity assay//Cell morphological analysis |
| Description: |
We found a gradual decrease in cell viability in NHOK, starting as low as 1 μM PAM, whereas an abrupt decrease was evident in NHOF at approximately 25 μM PAM.Using 10 μM PAM, we found a significant loss of proliferation in NHOK with rounded and flattened phenotypes .The cell cycle analysis revealed an increased S-phase content in response to both 10 and 50 μM PAM doses in NHOK .In PAM-treated NHOK, SA-β-gal activity increased up to 3.5-fold compared with that in the control, whereas no changes were observed in NHOF. |
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Regulatory relationship
| Regulatory pathway:
|
Mevalonate |
| Official symbol(s): |
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MVK
|
| Pathway experiment: |
MTT assay//SA-β-gal activity assay |
| Pathway description: |
We reconstituted geranylgeranylation and farnesylation using GGOH and FOH, respectively, and examined proliferation and senescence. Sublethal amounts of FOH, GGOH, and FOH/GGOH (1:0.5 ratio) were determined by MTT assay . Proliferation of PAM-treated NHOK was inhibited as expected. When NHOK were co-treated with PAM and FOH, similar results were observed; however, NHOK treated with PAM/GGOH or PAM/GGOH/FOH regained proliferative capacity by approximately half . When these cells were subjected to SA-β-gal staining, GGOH, but not FOH, reduced β-gal positivity by approximately half. Analysis of these data suggests that the senescence mechanism in PAM-treated NHOK is mediated, in part, through geranylgeranylation of the mevalonate pathway. |
Aging network
Annotation:
The green line represents Upregulation.
The purple line represents Downregulation.
The orange line represents Activation.
The yellow line represents Inhibition.
The gray line represents Unclear.