Multiple myeloma cell growth relies on intrinsic aggressiveness, due to a high karyotypic instability, or on the support from bone marrow (BM) niche.We and other groups have provided evidences that Notch signaling is related to tumor cell growth, pharmacological resistance, localization/recirculation in the BM and bone disease.This study indicates that high gene expression levels of Notch signaling members (JAG1, NOTCH2, HES5 and HES6) correlate with malignant progression or high-risk disease, and Notch signaling may participate in myeloma progression by increasing the BM levels of interleukin-6 (IL-6), a major player in myeloma cell growth and survival.
3) A network of disorders and disease genes linked by known disorder-gene associations indicates that cardiovascular disease and bone disease are closely related, suggesting that a single drug such as bisphosphonate, acting on a single gene, MMP2, could have both bone and cardiovascular side effects different from the osteoclast inhibition that is characteristic of bisphosphonate.
These findings identify a novel TRPV4 mutation implicating TRPV4 and altered calcium homeostasis in the pathogenesis of osteonecrosis while reinforcing the importance of TRPV4 in bone diseases and vascular endothelium.
The elucidation of HDAC complex components that influence Runx2 activity in specific cell types and in response to various extracellular stimuli will increase our understanding of how this crucial transcription factor functions, and how we might be able to control its activity to influence bone formation or reduce bone disease associated with cancer metastasis.
Among the discordant transcriptional profiles we identified two key mediators of vascular calcification and bone metabolism, ENPP1 and OPG, which offer a molecular explanation for the major phenotypic differences in vascular and bone disease in sporadic and hereditary HGPS.
A crosstalk between myeloma cells and marrow stromal cells stimulates production of DKK1 and interleukin-6: a potential role in the development of lytic bone disease and tumor progression in multiple myeloma.
Inhibition of FGF23 by burosumab results in increased renal phosphate reabsorption and increased serum levels of phosphorus and active vitamin D. In February 2018, the EMA granted subcutaneous burosumab conditional marketing authorization for the treatment of X-linked hypophosphataemia (XLH) with radiographic evidence of bone disease in children one year of age and older and adolescents with growing skeletons.
A new xenograft model of myeloma bone disease demonstrating the efficacy of human mesenchymal stem cells expressing osteoprotegerin by lentiviral gene transfer.
Furthermore, both TNF-α and IL-6 are important pathogenic factors related to immune-mediated bone diseases including rheumatoid arthritis and postmenopausal osteoporosis.
Collectively, this study demonstrates that Asiaticoside inhibited osteoclast formation and function through attenuating RANKL-induced key signaling pathways, which may indicate that Asiaticoside is a potential antiresorptive agent against osteoclast-related osteolytic bone diseases.
Using the 5T2MM murine model of MM we have previously shown that suppression of the activity of a known inhibitor of bone formation Dikkopf-1 (Dkk1) prevents the development of lytic bone disease.
PHP1B patients are at risk of developing tertiary hyperparathyroidism and/or hyperparathyroid bone disease and should therefore be treated with sufficient doses of calcium and vitamin D to achieve serum calcium and PTH levels within or as close to the normal range as possible.
Recombinant human OPG-Fc recognizes RANKL from multiple species and reduced bone resorption and increased bone volume, density, and strength in a number of rodent models of bone disease.
We found expression of potential FGF23 receptors ( Fgfr1-4) and α-Klotho in muscles of two animal models (CD-1 and Cy/+ rat, a naturally occurring rat model of chronic kidney disease-mineral bone disorder) as well as C<sub>2</sub>C<sub>12</sub> myoblasts and myotubes.
Relationships of Sclerostin, a bone anti-anabolic protein, with biomarkers of mineral bone disorders in chronic kidney disease are still unsettled, in particular in kidney transplant (KTR).
Myeloma cell expression of 10 candidate genes for osteolytic bone disease. Only overexpression of DKK1 correlates with clinical bone involvement at diagnosis.
In multiple myeloma (MM), aberrant auto-and/or paracrine activation of canonical Wnt signaling promotes proliferation and dissemination, while overexpression of the Wnt inhibitor Dickkopf1 (DKK1) by MM cells contributes to osteolytic bone disease by inhibiting osteoblast differentiation.