Osteocalcin Synthesis and Catabolism

描述（由申请人提供）：维生素K参与各种参与止血和骨和软骨代谢的蛋白质的生理激活。骨钙素是一种维生素k依赖性Ca2+结合蛋白，存在于骨和牙本质的有机基质中。循环骨钙素是一种高度特异性的成骨细胞标志物，已被广泛用于评估骨转换。本文提出的研究旨在验证测量骨钙素或其片段作为维生素K状态和骨转换指标的新方法。这些研究将评估：(1)通过钙动力学，骨钙素碎片的循环水平与骨增生和骨吸收之间的关系；(2)维生素K摄入对骨钙素循环形式的影响及其与其他骨转换指标的相关性。尽管骨钙素的功能尚未被精确定义，但在小鼠身上的研究表明，骨钙素可能在骨重塑中发挥作用。拟议的研究将(1)挽救骨钙素缺失小鼠（OC-/-），使其具有非羧化变体，这样骨钙素不会在骨骼中积累，但循环水平将升高。1,25(OH)2D3和卵巢切除术对wt、OC-/-和获救动物的影响将通过骨密度、矿物质含量、骨转换标志物、组织形态学参数和破骨细胞发育来评估。将在骨髓细胞中评估破骨细胞和/或成骨细胞祖细胞。

DESCRIPTION (provided by applicant): Vitamin K is involved in the physiological activation of various proteins involved in hemostasis and bone and cartilage metabolism. Osteocalcin is a vitamin K-dependent Ca2+binding protein found in the organic matrix of bone and dentin. Circulating osteocalcin is a highly specific osteoblastic marker and it has been widely used for assessing bone turnover. The studies proposed here seek to verify new methods for the measurement of osteocalcin or its fragments as indicators of vitamin K status and bone turnover. These studies will evaluate: (1) the relationship between circulating levels of osteocalcin fragments and bone accretion and resorption via calcium kinetics; and (2) the effect of vitamin K intake on the profile of circulating forms of osteocalcin and their correlation with other measures of bone turnover. Although, the function of osteocalcin has not been precisely defined, studies in mice suggest that osteocalcin may play a role in bone remodeling. The proposed studies will (1) rescue the osteocalcin null mouse (OC-/-) with an uncarboxylated variant such that osteocalcin will not accumulate in bone but circulating levels will be elevated. The effects of 1,25(OH)2D3 and ovariectomy in wt, OC-/- and rescued animals will be evaluated by bone density, mineral content, bone turnover markers histomorphometric parameters and osteoclast development. Osteoclast and/or osteoblast progenitors will be evaluated in bone marrow cells.