Rajakumar SA, Papp E, Grandal I, Merico D, Liu CC, Allo B, et al. RANK-RANKL mediated bone destruction in B-cell acute lymphoblastic leukemia.
These monocyte-derived osteoclasts then mediate bone destruction.
With Daedalus funding, Dr. Greenblatt will test the effects of SHN3 inhibitors in combination with bisphosphonates, the standard-of-care drugs used in some patients, to see if they improve outcomes in a mouse model of breast cancer-mediated bone destruction.
One interesting, currently evolving view is that low abundance periodontal pathogens orchestrate periodontitis by inducing a dysbiotic "pathogenic" microbial community that in turn mediates bone destruction [ 26].
MRP8/14 is a ligand to toll-like receptor 4 (TLR-4), has a pro-inflammatory effect on phagocytes and endothelial cells [ 6] and is an important factor in mediating osteoclastic bone destruction in experimental arthritis [ 7].
FLS can mediate cartilage and bone destruction in RA mainly via the elucidation of matrix metalloproteinases (MMPs) such as MMP-1 [ 3].
Moreover, TH mice expressed higher levels of a bone destruction mediating factor, RANKL, and a RANKL inducer, IL-6, in bone marrow.
IL-1β induces the production of MMP-3 in cell types such as FLS, chondrocytes, and macrophages in arthritic joints, and the subsequent elevated level of MMP-3 mediates cartilage and bone destruction, directly contributing to the pathogenesis of the disease [ 21].
It also prevented pathologic bone destruction mediated by tumor cells without affecting normal bone turnover or causing such unwanted effects as uncontrolled cell proliferation.
The SEM images revealed bone destruction mediated by osteoclasts (Figure 1F), whose activity may have been stimulated by pathogenic organisms.
