Elevation of fibrinogen due to loss of ovarian function enhances actin ring formation and leads to increased bone resorption
Autor: | Van Tien Phan, Ke Ke, Woon-Ki Kim, Hye-Seon Choi, Ok-Joo Sul, Mi-Hyun Lee, Hyun-Ju Kim, Shin-Yoon Kim |
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Rok vydání: | 2012 |
Předmět: |
Male
medicine.medical_specialty X-ray microtomography Cell Survival Physiology Ovariectomy Endocrinology Diabetes and Metabolism Cellular differentiation Osteoclasts Bone Marrow Cells Fibrinogen Statistics Nonparametric Mice Ovarian function Osteoclast Physiology (medical) Internal medicine medicine Animals Receptors Vitronectin Bone Resorption Receptor Cells Cultured Actin Analysis of Variance Chemistry Macrophage Colony-Stimulating Factor Intracellular Signaling Peptides and Proteins Cell Differentiation X-Ray Microtomography Actins Mice Inbred C57BL Postmenopause Actin Cytoskeleton Disease Models Animal medicine.anatomical_structure Endocrinology Increased bone resorption Osteoporosis Female Signal Transduction medicine.drug |
Zdroj: | American Journal of Physiology-Endocrinology and Metabolism. 303:E1296-E1303 |
ISSN: | 1522-1555 0193-1849 |
DOI: | 10.1152/ajpendo.00085.2012 |
Popis: | The aim of the present study was to evaluate the effect of fibrinogen on number and function of osteoclasts (OC) consequently resulting in bone loss. It was hypothesized that the enhanced level of released fibrinogen due to loss of ovarian function caused bone loss by acting on OCs. Bone loss was induced by ovariectomy (OVX) in mice and analyzed by micro-CT. The effect of fibrinogen on OCs was evaluated by tartrate-resistant acid phosphatase, annexin V, actin staining, pit formation observed on dentine slices, and Western blotting. Exogenous fibrinogen increased OC survival, actin ring formation, and bone resorption in vitro. The effect of fibrinogen was dependent on β3-integrin, which is a marker for mature OCs. Fibrinogen induced the activation of transforming oncogene from Ak strain (Akt), Ras-related C3 botulinum toxin substrate 1 (Rac1), and Rho family of GTPase (Rho) and the degradation of the Bcl-2 interacting mediator of cell death (Bim) in a manner similar to macrophage colony-stimulating factor (M-CSF). OVX increased plasma fibrinogen and serum M-CSF together with elevated actin ring formation and bone loss. The increased fibrinogen level due to loss of ovarian function may contribute, at least partly, to bone loss through the enhanced number and activity of OCs. |
Databáze: | OpenAIRE |
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