Published in:
01-09-2018 | Original Article
Bortezomib prevents ovariectomy-induced osteoporosis in mice by inhibiting osteoclast differentiation
Authors:
Sung-Hyun Kim, Myoung Ok Kim, Hyo Jeong Kim, Sanjiv Neupane, Hyung Joon Kim, Ji Hye Lee, Hong-Hee Kim, Jae-Young Kim, Youngkyun Lee
Published in:
Journal of Bone and Mineral Metabolism
|
Issue 5/2018
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Abstract
Bone homeostasis is achieved through coordinated activities of bone-forming osteoblasts and bone-resorbing osteoclasts. When the balance is skewed in favor of osteoclasts due to hormonal or inflammatory issues, pathologic bone loss occurs leading to conditions such as osteoporosis, rheumatoid arthritis, and periodontitis. Bortezomib is the first in-class of proteasome inhibitors used as an anti-myeloma agent. In the present study, we show that bortezomib directly inhibited the receptor activator of nuclear factor κB ligand (RANKL)—dependent osteoclast differentiation of mouse bone marrow macrophages. Bortezomib significantly reduced the induction of osteoclast marker genes and proteins including nuclear factor of activated T-cells, cytoplasmic 1 (NFATc1). The intraperitoneal injection of bortezomib reduced ovariectomy-induced osteoclastogenesis and protected the mice from bone loss. These data propose novel use of bortezomib as a potential anti-resorptive agent.