TY - JOUR
T1 - Proteasome Inhibitors and Bone Disease
AU - Qiang, Ya Wei
AU - Heuck, Christoph J.
AU - Shaughnessy, John D.
AU - Barlogie, Bart
AU - Epstein, Joshua
N1 - Funding Information:
Conflicts of interest: J.D.S. is co-founder of Myeloma Health LLC and owns stock in the company; he receives royalties from Novartis, Genzyme, and Myeloma Health, and he is a paid consultant to Novartis, Myeloma Health, Genzyme, Array BioPharma, Onyx, Millennium, and Celgene. B.B. has received research funding from Celgene and Novartis. He is a consultant to Celgene and Genzyme. He has received speaking honoraria from Celgene and Millennium. The other authors declare no competing financial interests.
Funding Information:
This research was supported by a Multiple Myeloma Research Foundation (MMRF) to Y.W.Q. and by a National Institutes of Health (NIH) P01 grant ( CA055819 ) to Y.W.Q., J.D.S., and B.B.
PY - 2012/7
Y1 - 2012/7
N2 - Bone disease in patients with multiple myeloma (MM) is characterized by increase in the numbers and activity of bone-resorpting osteoclasts and decrease in the number and function of bone-formation osteoblasts. MM-triggered inhibition of bone formation may stem from suppression of Wnt/β-catenin signaling, a pivotal pathway in the differentiation of mesenchymal stem cells (MSC) into osteoblasts, and regulating production of receptor activator of nuclear factor-κB ligand (RANKL)/osteoprotegerin (OPG) axis by osteoblasts. Proteasome inhibitors (PIs), such as bortezomib (Bz), induce activation of Wnt/β-catenin pathway and MSC differentiation toward osteoblasts. PIs also suppress osteoclastogenesis, possibly through regulating multiple pathways including NF-κB, Bim, and the ratio of RANKL/OPG. The critical role of PI in increasing osteoblast function and suppression of osteoclast activity is highlighted by clinical evidence of increases in bone formation and decreases in bone resorption makers. This review will discuss the function of PIs in stimulating bone formation and suppression of bone resorption, and the mechanism underlying this process that leads to inhibition bone disease in MM patients.
AB - Bone disease in patients with multiple myeloma (MM) is characterized by increase in the numbers and activity of bone-resorpting osteoclasts and decrease in the number and function of bone-formation osteoblasts. MM-triggered inhibition of bone formation may stem from suppression of Wnt/β-catenin signaling, a pivotal pathway in the differentiation of mesenchymal stem cells (MSC) into osteoblasts, and regulating production of receptor activator of nuclear factor-κB ligand (RANKL)/osteoprotegerin (OPG) axis by osteoblasts. Proteasome inhibitors (PIs), such as bortezomib (Bz), induce activation of Wnt/β-catenin pathway and MSC differentiation toward osteoblasts. PIs also suppress osteoclastogenesis, possibly through regulating multiple pathways including NF-κB, Bim, and the ratio of RANKL/OPG. The critical role of PI in increasing osteoblast function and suppression of osteoclast activity is highlighted by clinical evidence of increases in bone formation and decreases in bone resorption makers. This review will discuss the function of PIs in stimulating bone formation and suppression of bone resorption, and the mechanism underlying this process that leads to inhibition bone disease in MM patients.
UR - http://www.scopus.com/inward/record.url?scp=84862653565&partnerID=8YFLogxK
U2 - 10.1053/j.seminhematol.2012.04.011
DO - 10.1053/j.seminhematol.2012.04.011
M3 - Article
C2 - 22726547
AN - SCOPUS:84862653565
SN - 0037-1963
VL - 49
SP - 243
EP - 248
JO - Seminars in Hematology
JF - Seminars in Hematology
IS - 3
ER -