Accelerated growth plate mineralization and foreshortened proximal limb bones in fetuin-A knockout mice
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Accelerated growth plate mineralization and foreshortened proximal limb bones in fetuin-A knockout mice. / Seto, Jong; Busse, Björn; Gupta, Himadri S; Schäfer, Cora; Krauss, Stefanie; Dunlop, John W C; Masic, Admir; Kerschnitzki, Michael; Zaslansky, Paul; Boesecke, Peter; Catalá-Lehnen, Philip; Schinke, Thorsten; Fratzl, Peter; Jahnen-Dechent, Willi.
in: PLOS ONE, Jahrgang 7, Nr. 10, 01.01.2012, S. e47338.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - Accelerated growth plate mineralization and foreshortened proximal limb bones in fetuin-A knockout mice
AU - Seto, Jong
AU - Busse, Björn
AU - Gupta, Himadri S
AU - Schäfer, Cora
AU - Krauss, Stefanie
AU - Dunlop, John W C
AU - Masic, Admir
AU - Kerschnitzki, Michael
AU - Zaslansky, Paul
AU - Boesecke, Peter
AU - Catalá-Lehnen, Philip
AU - Schinke, Thorsten
AU - Fratzl, Peter
AU - Jahnen-Dechent, Willi
PY - 2012/1/1
Y1 - 2012/1/1
N2 - The plasma protein fetuin-A/alpha2-HS-glycoprotein (genetic symbol Ahsg) is a systemic inhibitor of extraskeletal mineralization, which is best underscored by the excessive mineral deposition found in various tissues of fetuin-A deficient mice on the calcification-prone genetic background DBA/2. Fetuin-A is known to accumulate in the bone matrix thus an effect of fetuin-A on skeletal mineralization is expected. We examined the bones of fetuin-A deficient mice maintained on a C57BL/6 genetic background to avoid bone disease secondary to renal calcification. Here, we show that fetuin-A deficient mice display normal trabecular bone mass in the spine, but increased cortical thickness in the femur. Bone material properties, as well as mineral and collagen characteristics of cortical bone were unaffected by the absence of fetuin-A. In contrast, the long bones especially proximal limb bones were severely stunted in fetuin-A deficient mice compared to wildtype littermates, resulting in increased biomechanical stability of fetuin-A deficient femora in three-point-bending tests. Elevated backscattered electron signal intensities reflected an increased mineral content in the growth plates of fetuin-A deficient long bones, corroborating its physiological role as an inhibitor of excessive mineralization in the growth plate cartilage matrix--a site of vigorous physiological mineralization. We show that in the case of fetuin-A deficiency, active mineralization inhibition is a necessity for proper long bone growth.
AB - The plasma protein fetuin-A/alpha2-HS-glycoprotein (genetic symbol Ahsg) is a systemic inhibitor of extraskeletal mineralization, which is best underscored by the excessive mineral deposition found in various tissues of fetuin-A deficient mice on the calcification-prone genetic background DBA/2. Fetuin-A is known to accumulate in the bone matrix thus an effect of fetuin-A on skeletal mineralization is expected. We examined the bones of fetuin-A deficient mice maintained on a C57BL/6 genetic background to avoid bone disease secondary to renal calcification. Here, we show that fetuin-A deficient mice display normal trabecular bone mass in the spine, but increased cortical thickness in the femur. Bone material properties, as well as mineral and collagen characteristics of cortical bone were unaffected by the absence of fetuin-A. In contrast, the long bones especially proximal limb bones were severely stunted in fetuin-A deficient mice compared to wildtype littermates, resulting in increased biomechanical stability of fetuin-A deficient femora in three-point-bending tests. Elevated backscattered electron signal intensities reflected an increased mineral content in the growth plates of fetuin-A deficient long bones, corroborating its physiological role as an inhibitor of excessive mineralization in the growth plate cartilage matrix--a site of vigorous physiological mineralization. We show that in the case of fetuin-A deficiency, active mineralization inhibition is a necessity for proper long bone growth.
KW - Animals
KW - Bone Density
KW - Bone Development
KW - Bone and Bones
KW - Calcification, Physiologic
KW - Growth Plate
KW - Mice
KW - Mice, Knockout
KW - alpha-2-HS-Glycoprotein
U2 - 10.1371/journal.pone.0047338
DO - 10.1371/journal.pone.0047338
M3 - SCORING: Journal article
C2 - 23091616
VL - 7
SP - e47338
JO - PLOS ONE
JF - PLOS ONE
SN - 1932-6203
IS - 10
ER -