Accelerated Growth Plate Mineralization and Foreshortened Proximal Limb Bones in Fetuin-A Knockout Mice
Authors
Seto, JongBusse, Bjorn
Gupta, Himadri S.
Schafer, Cora
Krauss, Stefanie
Dunlop, John W. C.
Masic, Admir
Kerschnitzki, Michael
Zaslansky, Paul
Boesecke, Peter
Catala-Lehnen, Philip
Schinke, Thorsten
Fratzl, Peter
Jahnen-Dechent, Willi
Issue Date
2012-10-16
Metadata
Show full item recordAbstract
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.Citation
PLoS One. 2012 Oct 16; 7(10):e47338ae974a485f413a2113503eed53cd6c53
10.1371/journal.pone.0047338
Scopus Count
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