title: Accelerated growth plate mineralization and foreshortened proximal limb bones in fetuin-A knockout mice.
abstract: 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.
authors.affiliation: Department of Biomaterials, Max Planck Institute of Colloids and Interfaces, Potsdam, Germany.
authors.forename: Jong
authors.initials: J
authors.lastname: Seto
authors.forename: Björn
authors.initials: B
authors.lastname: Busse
authors.forename: Himadri S
authors.initials: HS
authors.lastname: Gupta
authors.forename: Cora
authors.initials: C
authors.lastname: Schäfer
authors.forename: Stefanie
authors.initials: S
authors.lastname: Krauss
authors.forename: John W C
authors.initials: JW
authors.lastname: Dunlop
authors.forename: Admir
authors.initials: A
authors.lastname: Masic
authors.forename: Michael
authors.initials: M
authors.lastname: Kerschnitzki
authors.forename: Paul
authors.initials: P
authors.lastname: Zaslansky
authors.forename: Peter
authors.initials: P
authors.lastname: Boesecke
authors.forename: Philip
authors.initials: P
authors.lastname: Catalá-Lehnen
authors.forename: Thorsten
authors.initials: T
authors.lastname: Schinke
authors.forename: Peter
authors.initials: P
authors.lastname: Fratzl
authors.forename: Willi
authors.initials: W
authors.lastname: Jahnen-Dechent
mesh_terms: D000818:Animals; D015519:Bone Density / Q000235:genetics; D001846:Bone Development / Q000235:genetics; D001842:Bone and Bones / Q000378:metabolism* / Q000473:pathology; D002113:Calcification, Physiologic / Q000235:genetics*; D006132:Growth Plate / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D060749:alpha-2-HS-Glycoprotein / Q000235:genetics*
chemical_list: D060749:alpha-2-HS-Glycoprotein