Osteoporosis and inflammation.
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TLDR
RANKL expression is heightened in post- compared with pre-menopausal women, and this effect is attenuated by estrogen replacement therapy, and a human antibody with high specificity and affinity to RANKL is currently under clinical evaluation for the treatment of osteoporosis inPost- menopausal women and of metastatic bone disease in cancer patients with bone metastasis.Abstract:
Osteoporosis represents a major healthcare burden, affecting approximately 10 million people aged over 50 years in the United States and with another 30 million or more at risk. One of the major contributing factors to osteoporosis is withdrawal of estrogen during menopause in women. Human and animal experiments have implicated pro-inflammatory cy-tokines as primary mediators of the accelerated bone loss at menopause including interleukin-1, tumor necrosis factor-α, and interleukin-6. Increased production of pro-inflammatory cytokines is associated with osteoclastic bone resorption in a number of disease states including rheumatoid arthritis, periodontitis, and multiple myeloma; estrogen withdrawal is associated with increased production of pro-inflammatory cytokines, and exposure of bone cultures to supernatants from activated leukocytes is associated with increased bone resorption. A major advance has been the discovery ofRANKL, its receptor RANK, and the endogenous inhibitor osteoprotegerin. The binding of RANKL to RANK is essential for the differentiation and activation of osteoclasts and mediates the actions of essentially all known stimulators of osteoclastic bone resorption. RANKL expression is heightened in post- compared with pre-menopausal women, and this effect is attenuated by estrogen replacement therapy. RANKL is also a therapeutic target; a human antibody with high specificity and affinity to RANKL is currently under clinical evaluation for the treatment of osteoporosis in post-menopausal women and of metastatic bone disease in cancer patients with bone metastasis. Early data are promising.read more
Citations
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References
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Osteoprotegerin Ligand Is a Cytokine that Regulates Osteoclast Differentiation and Activation
David L. Lacey,Emma Timms,Hong-Lin Tan,Michael J. Kelley,Colin R. Dunstan,Tim Burgess,Robin Elliott,Anne Colombero,Gary Elliott,S. Scully,Hailing Hsu,John K. Sullivan,Nessa Hawkins,E. Davy,C. Capparelli,Alana Eli,Yi-xin Qian,Steve Kaufman,Ildiko Sarosi,Victoria Shalhoub,Giorgio Senaldi,Jane Guo,John M. Delaney,William J. Boyle +23 more
TL;DR: The effects of OPGL are blocked in vitro and in vivo by OPG, suggesting that OPGl and OPG are key extracellular regulators of osteoclast development.
Journal ArticleDOI
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Journal ArticleDOI
Osteoclast differentiation factor is a ligand for osteoprotegerin/osteoclastogenesis-inhibitory factor and is identical to TRANCE/RANKL
Hisataka Yasuda,Nobuyuki Shima,Nobuaki Nakagawa,Kyoji Yamaguchi,Masahiko Kinosaki,Shin Ichi Mochizuki,Akihiro Tomoyasu,Kazuki Yano,Masaaki Goto,Akihiko Murakami,Eisuke Tsuda,Tomonori Morinaga,Kanji Higashio,Nobuyuki Udagawa,Naoyuki Takahashi,Tatsuo Suda +15 more
TL;DR: In this article, a membrane-bound osteoclast differentiation factor (ODF) was found to induce OCL formation from osteoblasts/stromal cells in the presence of bone-resorbing factors.
Journal ArticleDOI
OPGL is a key regulator of osteoclastogenesis, lymphocyte development and lymph-node organogenesis
Young-Yun Kong,Hiroki Yoshida,Ildiko Sarosi,Hong-Lin Tan,Emma Timms,Casey Capparelli,Sean Morony,Antonio J. Oliveira-dos-Santos,Gwyneth Van,Annick Itie,Wilson Khoo,Andrew Wakeham,Colin R. Dunstan,David L. Lacey,Tak W. Mak,William J. Boyle,Josef M. Penninger +16 more
TL;DR: OPGL is a new regulator of lymph-node organogenesis and lymphocyte development and is an essential osteoclast differentiation factor in vivo.
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