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楼主 |
发表于 2009-5-22 23:19:22
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D1:
Inhibition of osteoblastic bone formation by nuclear factor-kB
This paper from nature medicine has presented us with plenty of logical evidence to demonstrate the important role of NF-kB in osteoblast, whose function is upregulated by inhibition of NF-kB in osteoblasts.
The structure of this paper is worth of learning.
step 1: by the construction of conditional NF-kB knockout mice, the authors verified the specific knockdown by southern blot, RT-PCR and western blot. Based on these results, they employed regular microCT and hisotological methods to demonstrate that the bone mineral density and bone volume is increased in these conditional knockout mice, which is due to the strengthened osteoblastic function, but not osteoclasts.
Then, they look into the signaling pathway involving NF-kB and confirmed this role of NF-kB in TNF induced phosphoration of degration of IKBalpha and phophoration of P65.What's more ,they verified this effect by rescue experiment by overexpressing p65 to activate NF-KB.
Then, they used OVX mice model to further confirm the role of NF-kB in osteoblasts during osteoporosis.
Finally, the author explored the molecular mechanism by analysis many involved pathways and find out the c-JUN and JNK were activated. again, they used RNAi to further confirm this conclusion.
In conclusion ,the logical analysis is worthy of learning. |
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