Isoform of fibronectin mediates bone loss in patients with primary biliary cirrhosis by suppressing bone formation
| Autor: | Anne Geursen, N. Kawelke, Anke Bentmann, Norman Hackl, Peter Feick, Inaam A. Nakchbandi, H. D. Hager, Manfred V. Singer |
|---|---|
| Rok vydání: | 2008 |
| Předmět: |
Male
medicine.medical_specialty Pathology Endocrinology Diabetes and Metabolism Osteoporosis Osteocalcin Liver disease Mice Primary biliary cirrhosis Calcification Physiologic Bone Density Osteogenesis Internal medicine medicine Animals Humans Protein Isoforms Orthopedics and Sports Medicine Bone Resorption Cells Cultured Osteoblasts biology Tibia business.industry Liver Cirrhosis Biliary Osteoblast Middle Aged medicine.disease Amniotic Fluid Fibronectins Osteopenia Fibronectin medicine.anatomical_structure Endocrinology biology.protein Female business Biomarkers Injections Intraperitoneal Calcification |
| Zdroj: | Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research. 23(8) |
| ISSN: | 1523-4681 |
| Popis: | Osteoporosis is a major cause of morbidity and decreased quality of life in patients with chronic cholestatic liver disease. It is established that this osteoporosis results from decreased bone formation, but the mechanisms for the interaction between liver and bone remain elusive. The aim of this study was to test the hypothesis that an increase in the production of cellular fibronectins during liver disease may result in decreased osteoblast-mediated mineralization and thus explain the decrease in bone formation. We performed a prospective cross-sectional study in patients with primary biliary cirrhosis and matched controls, followed by experiments on human and mouse osteoblasts in culture and injections in mice in vivo. In patients with primary biliary cirrhosis, the oncofetal domain of fibronectin correlated significantly with the decrease in osteocalcin, a marker of bone formation (r = -0.57, p < 0.05). In vitro, amniotic fluid fibronectin (aFN) containing mainly the oncofetal domain and EIIIA domain resulted in decreased osteoblast-mediated mineralization in human osteoblasts (69% decrease at 100 microg/ml; p < 0.01) and mouse osteoblasts (71% decrease; p < 0.05). Removing the EIIIA domain from aFN similarly suppressed mineralization by osteoblasts (78% decrease; p < 0.05). Injection of labeled aFN in mice showed that it infiltrates the bone, and its administration over 10 days resulted in decreased trabecular BMD (17% drop; p < 0.05), mineralizing surface (30% drop; p < 0.005), and number of osteoblasts (45% drop; p < 0.05). Increased production of a fibronectin isoform containing the oncofetal domain and its release in the circulation in patients with primary biliary cirrhosis is at least partially responsible for the decrease in bone formation seen in these patients. This establishes that a molecule that has thus far been viewed as an extracellular matrix protein exerts hormone-like actions. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Plný text