Saturday, April 18, 2009


The Role of Fetuin-A in Physiological and Pathological Mineralization

"A prototypic systemic inhibitor protein of mineralization [is] the hepatic plasma protein α2-Heremans-Schmid glycoprotein/fetuin-A. Fetuin-A mediates the formation of stable colloidal mineral–protein complexes called calciprotein particles (CPPs). Thus, fetuin-A is important in the stabilization and clearance of amorphous mineral precursor phases. Efficient clearance of CPPs and, thus, of excess mineral from circulation prevents local buildup of mineral and calcification of soft tissue. Besides calcium phosphate binding, fetuin-A also acts as a carrier for lipids, which may influence calcification, inflammation, and apoptosis. Fetuin-A-deficient (Ahsg −/−) mice show impaired growth of their long bones and premature growth plate closure. We posit that the absence of fetuin-A in the growth plate causes simultaneous lack of calcification inhibition and excess lipid hormone signaling, leading to premature growth plate mineralization and shortened long bones. Fetuin-A regulates endochondral ossification through mineralization inhibition and lipid (hormone) binding."

But can excessive amounts of Fetuin-A increase height?

"Fetuin-A inhibits trypsin"<-Fetuin-A also antagonizes(decreases) TGF-Beta signaling.

"In addition to an increased risk of ectopic calcification, Ahsg −/− mice have stunted femoral bones as well as increased cortical thickness and mechanical stability of these bones. This suggests a role for fetuin-A in endochondral bone formation beyond the established role in calcification inhibition"

"The growth plates of Ahsg −/− mice were disorganized, the number of chondrocyte columns was reduced, and unmineralized cartilage islands were present in the metaphysis."

Overexpression of fetuin-a counteracts ectopic mineralization in a mouse model of pseudoxanthoma elasticum (abcc6(-/-)).

"overexpression of fetuin-A in Abcc6(-/-) mice counteracts the ectopic mineralization. Delivery of an expression construct containing full-length mouse fetuin-A complementary DNA (cDNA), linked to a His-tag, to the liver of these mice resulted in elevated serum levels of this protein. As a consequence, soft tissue mineralization, which is a characteristic of Abcc6(-/-) mice, was reduced by approximately 70% at 12 weeks of age, but the effect was transient when examined 4 weeks later."

Unfortunately, no length data was obtained.

Fetuin-A and change in body composition in older persons.

Men and women aged 70-79 were studied.

Change in height after 5 years was "was −0.2 ± 2 cm"

Height data was measured but it's relationship to Fetuin-A was not presented :(

Fetuin A is also known as Alpha 2-HS-glycoprotein.

Alpha 2-HS-glycoprotein: expression in chondrocytes and augmentation of alkaline phosphatase and phospholipase A2 activity.

"The concentration of alpha 2-HS-glycoprotein dynamically changes in various physiological conditions and is highest in bone during growth. mRNA transcripts from growth zone and resting zone costochondral chondrocyte cultures hybridized with alpha 2-HS-glycoprotein cDNA. However, a difference of mRNA transcript size was observed, with chondrocyte mRNA transcripts being 2.2 kb, while mRNA isolated from liver was 1.6 kb. Presence of alpha 2-HS-glycoprotein in cartilage cells was found by immunohistochemical staining of human fetal epiphyses using anti-human alpha 2-HS-glycoprotein antibody. To understand the role of alpha 2-HS-glycoprotein in cartilage growth, the effects of exogenous alpha 2-HS-glycoprotein were correlated with alkaline phosphatase (ALPase) and phospholipase A2 (PA2) activity in the chondrocyte cultures. Alkaline phosphatase specific activity was stimulated by alpha 2-HS-glycoprotein at concentrations between 0.25 and 1.25 micrograms/mL in the growth zone and resting zone cultures 2.7 and 2.0-fold, respectively. Matrix vesicle PA2 activity was increased only in the growth zone chondrocyte cultures. These results suggested that alpha 2-HS-glycoprotein may contribute to the regulation of the expression of the chondrocyte phenotype. Steady state mRNA levels of ALPase were analyzed in chondrocytes after additions of alpha 2-HS-glycoprotein. The ALPase mRNA levels remained stationary during the stimulation of enzymatic activity, indicating that the effect of alpha 2-HS-glycoprotein upon alkaline phosphatase activity is not at the transcriptional level."

Couldn't connect to this study right now.

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