Sclerostin Levels Associated with Inhibition of the Wnt/β-Catenin Signaling and Reduced Bone Turnover in Type 2 Diabetes Mellitus

Context: Patients with type 2 diabetes (T2DM) have low bone turnover, poor bone quality, and circulating levels of sclerostin significantly higher than non-T2DM controls. There are no data on the possible association of sclerostin with β-catenin, a key component of the Wnt/β-catenin canonical signal...

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Veröffentlicht in:The journal of clinical endocrinology and metabolism 2012-10, Vol.97 (10), p.3744-3750
Hauptverfasser: Gaudio, Agostino, Privitera, Filippo, Battaglia, Katia, Torrisi, Venerando, Sidoti, Maria Helga, Pulvirenti, Ivana, Canzonieri, Elena, Tringali, Giovanni, Fiore, Carmelo Erio
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container_issue 10
container_start_page 3744
container_title The journal of clinical endocrinology and metabolism
container_volume 97
creator Gaudio, Agostino
Privitera, Filippo
Battaglia, Katia
Torrisi, Venerando
Sidoti, Maria Helga
Pulvirenti, Ivana
Canzonieri, Elena
Tringali, Giovanni
Fiore, Carmelo Erio
description Context: Patients with type 2 diabetes (T2DM) have low bone turnover, poor bone quality, and circulating levels of sclerostin significantly higher than non-T2DM controls. There are no data on the possible association of sclerostin with β-catenin, a key component of the Wnt/β-catenin canonical signaling. Objectives: The aim of the study was to evaluate the circulating β-catenin levels in T2DM patients and to analyze their relationship with sclerostin and bone turnover markers. Design: This was a cross-sectional study. Setting and Patients: The study was conducted at a clinical research center. Forty T2DM postmenopausal women were studied and compared with 40 healthy controls. Bone status was assessed by dual-energy x-ray absorptiometry measurements (bone mineral density) and by measuring bone alkaline phosphatase and carboxy-terminal telopeptide of type 1 collagen. Sclerostin and β-catenin were evaluated by an immunoenzymetric assay. Results: Consistent with previous reports in T2DM subjects, we found sclerostin levels higher and bone turnover markers lower than controls. In our cohort of T2DM patients, β-catenin levels are significantly lower than in controls (median 1.22 pg/ml, 25th to 75th percentiles 0.50–2.80; and median 4.25 pg/ml, 25th to 75th percentiles 2.20–7.62, respectively; P = 0.0002). β-Catenin correlated negatively with sclerostin (P < 0.0001) and positively with bone alkaline phosphatase (P = 0.0030) only in T2DM patients and negatively with age in both groups. Eight of the 40 T2DM patients had vertebral fractures. Conclusions: These results show for the first time that T2DM patients have serum concentrations of β-catenin lower than controls. The negative association of β-catenin with sclerostin suggests a biological effect of increased sclerostin on the Wnt signaling, which appears impaired in T2DM.
doi_str_mv 10.1210/jc.2012-1901
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There are no data on the possible association of sclerostin with β-catenin, a key component of the Wnt/β-catenin canonical signaling. Objectives: The aim of the study was to evaluate the circulating β-catenin levels in T2DM patients and to analyze their relationship with sclerostin and bone turnover markers. Design: This was a cross-sectional study. Setting and Patients: The study was conducted at a clinical research center. Forty T2DM postmenopausal women were studied and compared with 40 healthy controls. Bone status was assessed by dual-energy x-ray absorptiometry measurements (bone mineral density) and by measuring bone alkaline phosphatase and carboxy-terminal telopeptide of type 1 collagen. Sclerostin and β-catenin were evaluated by an immunoenzymetric assay. Results: Consistent with previous reports in T2DM subjects, we found sclerostin levels higher and bone turnover markers lower than controls. In our cohort of T2DM patients, β-catenin levels are significantly lower than in controls (median 1.22 pg/ml, 25th to 75th percentiles 0.50–2.80; and median 4.25 pg/ml, 25th to 75th percentiles 2.20–7.62, respectively; P = 0.0002). β-Catenin correlated negatively with sclerostin (P &lt; 0.0001) and positively with bone alkaline phosphatase (P = 0.0030) only in T2DM patients and negatively with age in both groups. Eight of the 40 T2DM patients had vertebral fractures. Conclusions: These results show for the first time that T2DM patients have serum concentrations of β-catenin lower than controls. 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There are no data on the possible association of sclerostin with β-catenin, a key component of the Wnt/β-catenin canonical signaling. Objectives: The aim of the study was to evaluate the circulating β-catenin levels in T2DM patients and to analyze their relationship with sclerostin and bone turnover markers. Design: This was a cross-sectional study. Setting and Patients: The study was conducted at a clinical research center. Forty T2DM postmenopausal women were studied and compared with 40 healthy controls. Bone status was assessed by dual-energy x-ray absorptiometry measurements (bone mineral density) and by measuring bone alkaline phosphatase and carboxy-terminal telopeptide of type 1 collagen. Sclerostin and β-catenin were evaluated by an immunoenzymetric assay. Results: Consistent with previous reports in T2DM subjects, we found sclerostin levels higher and bone turnover markers lower than controls. In our cohort of T2DM patients, β-catenin levels are significantly lower than in controls (median 1.22 pg/ml, 25th to 75th percentiles 0.50–2.80; and median 4.25 pg/ml, 25th to 75th percentiles 2.20–7.62, respectively; P = 0.0002). β-Catenin correlated negatively with sclerostin (P &lt; 0.0001) and positively with bone alkaline phosphatase (P = 0.0030) only in T2DM patients and negatively with age in both groups. Eight of the 40 T2DM patients had vertebral fractures. Conclusions: These results show for the first time that T2DM patients have serum concentrations of β-catenin lower than controls. 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Impaired glucose tolerance</topic><topic>Endocrine pancreas. Apud cells (diseases)</topic><topic>Endocrinopathies</topic><topic>Etiopathogenesis. Screening. Investigations. Target tissue resistance</topic><topic>Feeding. Feeding behavior</topic><topic>Female</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Genetic Markers</topic><topic>Humans</topic><topic>Medical sciences</topic><topic>Middle Aged</topic><topic>Osteoporosis - epidemiology</topic><topic>Osteoporosis - metabolism</topic><topic>Risk Factors</topic><topic>Spinal Fractures - epidemiology</topic><topic>Spinal Fractures - metabolism</topic><topic>Vertebrates: anatomy and physiology, studies on body, several organs or systems</topic><topic>Vertebrates: endocrinology</topic><topic>Wnt Signaling Pathway - physiology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Gaudio, Agostino</creatorcontrib><creatorcontrib>Privitera, Filippo</creatorcontrib><creatorcontrib>Battaglia, Katia</creatorcontrib><creatorcontrib>Torrisi, Venerando</creatorcontrib><creatorcontrib>Sidoti, Maria Helga</creatorcontrib><creatorcontrib>Pulvirenti, Ivana</creatorcontrib><creatorcontrib>Canzonieri, Elena</creatorcontrib><creatorcontrib>Tringali, Giovanni</creatorcontrib><creatorcontrib>Fiore, Carmelo Erio</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>Calcium &amp; Calcified Tissue Abstracts</collection><jtitle>The journal of clinical endocrinology and metabolism</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Gaudio, Agostino</au><au>Privitera, Filippo</au><au>Battaglia, Katia</au><au>Torrisi, Venerando</au><au>Sidoti, Maria Helga</au><au>Pulvirenti, Ivana</au><au>Canzonieri, Elena</au><au>Tringali, Giovanni</au><au>Fiore, Carmelo Erio</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Sclerostin Levels Associated with Inhibition of the Wnt/β-Catenin Signaling and Reduced Bone Turnover in Type 2 Diabetes Mellitus</atitle><jtitle>The journal of clinical endocrinology and metabolism</jtitle><addtitle>J Clin Endocrinol Metab</addtitle><date>2012-10</date><risdate>2012</risdate><volume>97</volume><issue>10</issue><spage>3744</spage><epage>3750</epage><pages>3744-3750</pages><issn>0021-972X</issn><eissn>1945-7197</eissn><coden>JCEMAZ</coden><abstract>Context: Patients with type 2 diabetes (T2DM) have low bone turnover, poor bone quality, and circulating levels of sclerostin significantly higher than non-T2DM controls. There are no data on the possible association of sclerostin with β-catenin, a key component of the Wnt/β-catenin canonical signaling. Objectives: The aim of the study was to evaluate the circulating β-catenin levels in T2DM patients and to analyze their relationship with sclerostin and bone turnover markers. Design: This was a cross-sectional study. Setting and Patients: The study was conducted at a clinical research center. Forty T2DM postmenopausal women were studied and compared with 40 healthy controls. Bone status was assessed by dual-energy x-ray absorptiometry measurements (bone mineral density) and by measuring bone alkaline phosphatase and carboxy-terminal telopeptide of type 1 collagen. Sclerostin and β-catenin were evaluated by an immunoenzymetric assay. Results: Consistent with previous reports in T2DM subjects, we found sclerostin levels higher and bone turnover markers lower than controls. In our cohort of T2DM patients, β-catenin levels are significantly lower than in controls (median 1.22 pg/ml, 25th to 75th percentiles 0.50–2.80; and median 4.25 pg/ml, 25th to 75th percentiles 2.20–7.62, respectively; P = 0.0002). β-Catenin correlated negatively with sclerostin (P &lt; 0.0001) and positively with bone alkaline phosphatase (P = 0.0030) only in T2DM patients and negatively with age in both groups. Eight of the 40 T2DM patients had vertebral fractures. Conclusions: These results show for the first time that T2DM patients have serum concentrations of β-catenin lower than controls. The negative association of β-catenin with sclerostin suggests a biological effect of increased sclerostin on the Wnt signaling, which appears impaired in T2DM.</abstract><cop>Bethesda, MD</cop><pub>Endocrine Society</pub><pmid>22855334</pmid><doi>10.1210/jc.2012-1901</doi><tpages>7</tpages><oa>free_for_read</oa></addata></record>
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subjects Aged
beta Catenin - metabolism
Biological and medical sciences
Biomarkers - metabolism
Bone Density - physiology
Bone Morphogenetic Proteins - blood
Bone Remodeling - physiology
Cross-Sectional Studies
Diabetes Mellitus, Type 2 - epidemiology
Diabetes Mellitus, Type 2 - metabolism
Diabetes. Impaired glucose tolerance
Endocrine pancreas. Apud cells (diseases)
Endocrinopathies
Etiopathogenesis. Screening. Investigations. Target tissue resistance
Feeding. Feeding behavior
Female
Fundamental and applied biological sciences. Psychology
Genetic Markers
Humans
Medical sciences
Middle Aged
Osteoporosis - epidemiology
Osteoporosis - metabolism
Risk Factors
Spinal Fractures - epidemiology
Spinal Fractures - metabolism
Vertebrates: anatomy and physiology, studies on body, several organs or systems
Vertebrates: endocrinology
Wnt Signaling Pathway - physiology
title Sclerostin Levels Associated with Inhibition of the Wnt/β-Catenin Signaling and Reduced Bone Turnover in Type 2 Diabetes Mellitus
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