Journal ArticleDOI
Increased osteoclast development after estrogen loss: mediation by interleukin-6
Robert L. Jilka,Giao Hangoc,Giuseppe Girasole,Giovanni Passeri,Daniel C. Williams,John S. Abrams,Brendan F. Boyce,Hal E. Broxmeyer,Stavros C. Manolagas +8 more
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TLDR
Estrogen loss results in an interleukin-6-mediated stimulation of osteoclastogenesis, which suggests a mechanism for the increased bone resorption in postmenopausal osteoporosis.Abstract:
Osteoclasts, the cells that resorb bone, develop from hematopoietic precursors of the bone marrow under the control of factors produced in their microenvironment. The cytokine interleukin-6 can promote hematopoiesis and osteoclastogenesis. Interleukin-6 production by bone and marrow stromal cells is suppressed by 17 beta-estradiol in vitro. In mice, estrogen loss (ovariectomy) increased the number of colony-forming units for granulocytes and macrophages, enhanced osteoclast development in ex vivo cultures of marrow, and increased the number of osteoclasts in trabecular bone. These changes were prevented by 17 beta-estradiol or an antibody to interleukin-6. Thus, estrogen loss results in an interleukin-6-mediated stimulation of osteoclastogenesis, which suggests a mechanism for the increased bone resorption in postmenopausal osteoporosis.read more
Citations
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IL-6 in Inflammation, Immunity, and Disease
TL;DR: The mechanism for the continual synthesis of IL-6 needs to be elucidated to facilitate the development of more specific therapeutic approaches and analysis of the pathogenesis of specific diseases.
Journal ArticleDOI
osteoprotegerin-deficient mice develop early onset osteoporosis and arterial calcification
N. Bucay,Ildiko Sarosi,Colin R. Dunstan,Sean Morony,John E. Tarpley,C. Capparelli,S. Scully,Hong Lin Tan,Weilong Xu,David L. Lacey,William J. Boyle,William S. Simonet +11 more
TL;DR: It is demonstrated that OPG is a critical regulator of postnatal bone mass and regulation of OPG, its signaling pathway, or its ligand(s) may play a role in the long observed association between osteoporosis and vascular calcification.
Journal ArticleDOI
Birth and death of bone cells: basic regulatory mechanisms and implications for the pathogenesis and treatment of osteoporosis.
TL;DR: The role and the molecular mechanism of action of regulatory molecules, such as cytokines and hormones, in osteoclast and osteoblast birth and apoptosis are reviewed to review the evidence for the contribution of changes in bone cell birth or death to the pathogenesis of the most common forms of osteoporosis.
Journal ArticleDOI
Stimulation of bone formation in vitro and in rodents by statins.
Gregory R. Mundy,R I Garrett,Stephen E. Harris,J. Chan,David J. Chen,G. Rossini,Brendan F. Boyce,Ming Zhao,Gloria Gutierrez +8 more
TL;DR: It is shown that the statins, drugs widely used for lowering serum cholesterol, also enhance new bone formation in vitro and in rodents, and may have therapeutic applications for the treatment of osteoporosis.
Journal ArticleDOI
Increased bone formation in osteocalcin-deficient mice
Patricia Ducy,Christelle Desbois,Brendan F. Boyce,Gerald J. Pinero,Beryl Story,Colin R. Dunstan,Erica Smith,Jeffrey Bonadio,Steven A. Goldstein,Caren M. Gundberg,Allan Bradley,Gerard Karsenty +11 more
TL;DR: This study provides the first evidence that osteocalcin is a determinant of bone formation, and generates osteocalin-deficient mice that develop a phenotype marked by higher bone mass and bones of improved functional quality.
References
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The ovariectomized rat model of postmenopausal bone loss
TL;DR: Ovariectomy induced bone loss in the rat and postmenopausal bone loss share many similar characteristics, including: increased rate of bone turnover with resorption exceeding formation; and initial rapid phase of bone loss followed by a much slower phase.
Journal ArticleDOI
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TL;DR: Results indicate that osteoblastic cells are required for the differentiation of osteoclast progenitors in splenic tissues into multinucleated osteoclasts.
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Long-term prevention of postmenopausal osteoporosis by œstrogen
TL;DR: In this paper, the bone mineral content of oophorectomised women with Stochastic Hormone Replacement (SHR) was found to increase bone mineral levels during the first three years of treatment.
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Outcome for infants of very low birthweight: survey of world literature.
TL;DR: Reports from developed countries world wide describing the outcome for infants of very low birthweight born since 1946 show that, in general, mortality rates and the prevalence of major handicap in survivors were high until 1960, whereas the handicap-rate has remained stable and relatively low at 6--8% of VLBW live births.
Journal ArticleDOI
17 beta-estradiol inhibits interleukin-6 production by bone marrow-derived stromal cells and osteoblasts in vitro: a potential mechanism for the antiosteoporotic effect of estrogens.
G. Girasole,Robert L. Jilka,G. Passeri,S. Boswell,G. Boder,D.C. Williams,Stavros C. Manolagas,Stavros C. Manolagas +7 more
TL;DR: In vitro evidence suggests, for the first time, a mechanistic paradigm by which estrogens might exert at least part of their antiresorptive influence on the skeleton.