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Inhibition of cathepsin K may therefore prevent bone resorption, as could be demonstrated in bone metastasis from breast cancer [ 16].
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Lipotoxicity has been demonstrated in bone cells in vitro using osteoblasts and adipocytes in coculture.
Vitamin D has been demonstrated in bone marrow to affect marrow function [ 12, 13].
No evidence of woven bone, marrow fibrosis, or cellular toxicity was demonstrated in bone biopsies from these patients.
29, 37 Accordingly, restoration of p15ink4b expression through hypomethylation has been demonstrated in bone marrow cells from MDS patients treated with decitabine.
Whilst we have shown the mutant IFITM5 gene is transcribed in human bone, the longer form of IFITM5 protein has not yet been demonstrated in bone; this will be challenging in human bone due to scarcity of clinical sample.
Moreover, a link between IFN-γ and RANKL signalling via TRAF6 has also been demonstrated in bone marrow cultures in which IFN-γ was shown to accelerate the degradation of TRAF6 [ 27].
A link between IFN-γ and RANK signaling via TRAF6 has also been demonstrated in bone marrow cultures, in which IFN-γ was shown to accelerate the degradation of TRAF6 [ 38].
Phosphorylation of Akt has been demonstrated in bone marrow biopsies from MM patients, whereas PI3K signalling is activated in response to agents that promote survival, and/or chemoresistance, including IL-6, IGF-1, BAFF (B-cell activating factor)/APRIL (A proliferation-inducing ligand), and adhesion to extracellular matrix.
Such data have yet to be demonstrated in humans with bone metastases.
By removing blood, marrow, and fat from the bone graft, improved bone graft incorporation has been demonstrated in a bone chamber model in goats (Van der Donk et al. 2003).
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