Details der Publikation - Isoform of fibronectin mediates bone loss in patients with primary biliary cirrhosis by suppressing bone formation

Isoform of fibronectin mediates bone loss in patients with primary biliary cirrhosis by suppressing bone formation / Nina Kawelke, Anke Bentmann, Norman Hackl, Hans-Dieter Hager, Peter Feick, Anne Geursen, Manfred V. Singer, and Inaam A. Nakchbandi

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..

Medienart:	E-Artikel

Erscheinungsjahr:	March 17, 2008 2008
Erschienen:	March 17, 2008

Enthalten in:	Zur Gesamtaufnahme - volume:23
Enthalten in:	Journal of bone and mineral research - 23(2008), 8, Seite 1278-1286

Sprache:	Englisch

Beteiligte Personen:	Kawelke, Nina [VerfasserIn] Bentmann, Anke, 1980- [VerfasserIn] Hackl, Norman J. [VerfasserIn] Hager, Hans-Dieter [VerfasserIn] Feick, Peter, 1956- [VerfasserIn] Geursen, Anne, 1978- [VerfasserIn] Singer, Manfred V., 1945- [VerfasserIn] Nakchbandi, Inaam, 1967- [VerfasserIn]

Links:	Volltext [lizenzpflichtig] Volltext [lizenzpflichtig]

Themen:	Amniotic Fluid Animals Biomarkers Bone Density Bone Resorption Calcification, Physiologic Cells, Cultured Female Fibronectins Humans Injections, Intraperitoneal Liver Cirrhosis, Biliary Male Mice Middle Aged Osteoblasts Osteocalcin Osteogenesis Protein Isoforms Tibia

Anmerkungen:	Gesehen am 30.06.2021

Umfang:	9

doi:	10.1359/jbmr.080313

funding:
Förderinstitution / Projekttitel:

PPN (Katalog-ID):	1761588494

Internformat


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245	1	0	\|a Isoform of fibronectin mediates bone loss in patients with primary biliary cirrhosis by suppressing bone formation \|c Nina Kawelke, Anke Bentmann, Norman Hackl, Hans-Dieter Hager, Peter Feick, Anne Geursen, Manfred V. Singer, and Inaam A. Nakchbandi
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520			\|a 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.
650		4	\|a Amniotic Fluid
650		4	\|a Animals
650		4	\|a Biomarkers
650		4	\|a Bone Density
650		4	\|a Bone Resorption
650		4	\|a Calcification, Physiologic
650		4	\|a Cells, Cultured
650		4	\|a Female
650		4	\|a Fibronectins
650		4	\|a Humans
650		4	\|a Injections, Intraperitoneal
650		4	\|a Liver Cirrhosis, Biliary
650		4	\|a Male
650		4	\|a Mice
650		4	\|a Middle Aged
650		4	\|a Osteoblasts
650		4	\|a Osteocalcin
650		4	\|a Osteogenesis
650		4	\|a Protein Isoforms
650		4	\|a Tibia
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Isoform of fibronectin mediates bone loss in patients with primary biliary cirrhosis by suppressing bone formation / Nina Kawelke, Anke Bentmann, Norman Hackl, Hans-Dieter Hager, Peter Feick, Anne Geursen, Manfred V. Singer, and Inaam A. Nakchbandi

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