Studies of the role of nf-κb in controlling osteoclast differentiation and bone loss
Yao, Z. 2016. Studies of the role of nf-κb in controlling osteoclast differentiation and bone loss. PhD thesis University of Westminster Biomedical Sciences
Yao, Z. 2016. Studies of the role of nf-κb in controlling osteoclast differentiation and bone loss. PhD thesis University of Westminster Biomedical Sciences
Title | Studies of the role of nf-κb in controlling osteoclast differentiation and bone loss |
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Type | PhD thesis |
Authors | Yao, Z. |
Abstract | Increased osteoclast (OC) bone resorption and/or decreased osteoblast (OB) bone formation contribute to bone loss in osteoporosis and rheumatoid arthritis (RA). Findings of the basic and translational research presented in this thesis demonstrate a number of mechanisms by which cytokine-induced NF-κB activation controls bone resorption and formation: 1) Tumour necrosis factor-α (TNF) expands pool of OC precursors (OCPs) by promoting their proliferation through stimulation of the expression of macrophage colony stimulating factor (M-CSF) receptor, c-Fms, and switching M-CSF-induced resident (M2) to inflammatory (M1) macrophages with enhanced OC forming potential and increased production of inflammatory factors through induction of NF-κB RelB; 2) Similar to RANKL, TNF sequentially activates transcriptional factors NF-κB p50 and p52 followed by c-Fos and then NFATc1 to induce OC differentiation. However, TNF alone nduces very limited OC differentiation. In contrast, it pre-activates OCPs to express cFos which cooperates with interleukin-1 (IL-1) produced by these OCPs in an autocrine mechanism by interacting with bone matrix to mediate the OC terminal differentiation and bone resorption from these pre-activated OCPs. 3) TNF-induced OC formation is independent of RANKL but it also induces NF-κB2 p100 to limit OC formation and bone |
Year | 2016 |
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