BONE METABOLISM
Gla-proteins
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All three bone Gla-proteins presently known are synthesized by the osteoblasts (the bone forming cells), but only osteocalcin is a unique product of bone tissue. Protein S and MGP are also synthesized in a number of soft tissues including the vessel wall (see vascular biology). Osteocalcin represents about 20% of the non-collagenous proteins in bone and is one of the most abundant proteins in humans. The precise function of the bone Gla-proteins is not yet clear. Osteocalcin-deficient mice turned out to grow more rapidly than the wild types, showing that osteocalcin is a negative regulator of bone formation. Furthermore, histomorphometric studies revealed that the absence of osteocalcin leads to an increased bone formation and improved quality without impairing bone resporption. Also for MGP knock-out mice have been generated. These animals showed substantial growth retardation, with excessive calcifications of their growth plates, osteopenia and bone fractures. Since all animals died from cardiovascular disease within 2 months after birth (see below) long term effects of MGP-deficiency on bone are still unknown. Recently, it was reported that in three independent cases the human Keutel syndrome is associated with a DNA mutation leading to the expression of non-functional MGP. Keutel syndrome is an autosomal recessive disorder characterized by abnormal cartilage calcification, peripheral pulmonary stenosis, short terminal phalanges, abnormal cartilage calcification of the auricles, nose, larynx, trachea and ribs, and by mid-facial hypoplasia with a depressed nasal bridge. Recommended literature:
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