These monocyte-derived osteoclasts then mediate bone destruction.
Established roles for the Pim kinases in MM are diverse and include MM proliferation, survival, cell cycle dysregulation, an oncogenic collaboration with the most frequently dysregulated gene in MM (Myc) and mediating 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].
Moreover, in experimental periodontitis, PGE2 has been shown to exacerbate the disease, in contrast to the structurally related lipid mediator resolvin E1, which has been shown to protect from osteoclast-mediated bone destruction and restore tissue homeostasis in a rabbit model (29, 30).
It was highly expected that pyogenic S. aureus infections with progressive enzyme-mediated bone destruction result on a high local accumulation of 18 F-FDG because the tracer uptake is known to be elevated in activated leucocytes, granulocytes, and macrophages.
These factors stimulate osteoclast-mediated bone destruction leading to increased bone lesions compared to control mice [ 57].
The delicate balance between osteoclast-mediated bone destruction and osteoblast-mediated bone formation is important for maintaining bone mineral density.
Multiple myeloma, a cancer of plasma cells, is associated with excessive tumor-induced, osteoclast-mediated bone destruction.
Additional studies would be needed to determine how Treg cells affect osteoclast-mediated bone destruction under inflammatory conditions.
