Accelerated growth plate mineralization and foreshortened proximal limb bones in fetuin-A knockout mice

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 -