Osteocalcin Synthesis and Catabolism - Caren Gundberg
Osteocalcin synthesis essay - MyOrganicRecipes
Osteocalcin is a hormonally regulated calcium-binding protein made almost exclusively by osteoblasts. In normal cells, osteocalcin expression requires ascorbic acid (AA), an essential cofactor for osteoblast differentiation both in vivo and in vitro. To determine the mechanism of this regulation, subclones of MC3T3-E1 preosteoblasts were transiently transfected with 1.3 kb of the mouse osteocalcin gene 2 promoter driving expression of firefly luciferase. AA stimulated luciferase activity 20-fold after 4-5 days. This response was stereospecific to L-ascorbic acid and was only detected in MC3T3-E1 subclones showing strong AA induction of the endogenous osteocalcin gene. Similar results were also obtained in MC3T3-E1 cells stably transfected with the osteocalcin promoter. A specific inhibitor of collagen synthesis, 3,4-dehydroproline, blocked AA-dependent induction of promoter activity, indicating that regulation of the osteocalcin gene requires collagen matrix synthesis. Deletion analysis of the mOG2 promoter identified an essential region for AA responsiveness between -147 and -116 bp. This region contains a single copy of the previously described osteoblast-specific element, OSE2. Deletion and mutation of OSE2 in DNA transfection assays established the requirement for this element in the AA response. Furthermore, DNA-binding assays revealed that MC3T3-E1 cells contain OSF2, the nuclear factor binding to OSE2, and that binding of OSF2 to OSE2 is up-regulated by AA treatment. Taken collectively, our results indicate that an intact OSE2 sequence is required for the induction of osteocalcin expression by AA.
Regulation by Heat Shock Protein 27 of Osteocalcin Synthesis in ..
Kanno Y, Ishisaki A, Yoshida M, NakajimaK, Tokuda H, Numata O and Kozawa O: Adenylyl cyclase-cAMP systeminhibits thyroid hormone-stimulated osteocalcin synthesis inosteoblasts. Mol Cell Endocrinol. 229:75–82. 2005. : :
Osteocalcin: An Endocrine Link Between Bone and …
Bone metabolism is strictly regulated byosteoblastic bone formation and osteoclastic bone resorption(). Bone tissue is continuouslyregenerated through a process known as bone remodeling. This boneremodeling process begins with osteoclastic bone resorption,followed by osteoblastic bone formation (). It is generally established thatosteoblasts play a crucial role in the regulation of boneresorption through the expression of the receptor activator ofnuclear factor κB ligand (RANKL) in response to a variety of boneresorptive stimuli (). Osteoblastsexpress various cell type-specific markers during theirdifferentiation process. Osteocalcin, which is synthesized byosteoblasts and recognized as a marker of mature osteoblastphenotype, is the most abundant non-collagenous protein (). It is generally known that osteocalcin ispost-translationally modified by vitamin K-dependentγ-carboxylation as bone Gla-protein (). It has been reported thatosteocalcin-deficient mice develop an increase of bone formationwithout impairing bone resorption, suggesting that osteocalcin is adeterminant of bone formation (). Inaddition, uncarboxylated osteocalcin functions as a potent hormone,which regulates energy metabolism by stimulating the insulinsecretion from β-cells of pancreatic islets and upregulating theinsulin sensitivity of peripheral organs such as muscle and adipose(). Thus, bone is currentlyrecognized to act as an endocrine organ through the release ofosteocalcin.
Jun 05, 2014 · Osteocalcin is a noncollagenous, ..
The thyroid hormone acts as an important regulatorin the skeletal function as well as whole-body metabolism. Anexcess of thyroid hormone, known as hyperthyroidism, upregulatesthe bone metabolic turnover and increases the ratio of boneresorption to bone formation, resulting in osteoporosis associatedwith an increased risk of bone fracture (). It has been reported that bone mineraldensity is markedly decreased in untreated patients ofhyperthyroidism (). The receptor ofthyroid hormone belongs to the nuclear receptor superfamily(). The biological functions of thethyroid hormone are mainly mediated by binding to specificreceptors in the nucleus, and that the receptor-hormone complexactivates the transcription of related genes (). In osteoblasts, the thyroid hormonestimulates alkaline phosphatase activity and modulates theproliferation of osteoblasts ().Previously, we showed that triiodothyronine (T)stimulates osteocalcin synthesis at least in part via p38mitogen-activated protein (MAP) kinase in osteoblast-like MC3T3-E1cells and that the adenylyl cyclase-cAMP system regulates theosteocalcin synthesis via the suppression of p38 MAP kinaseactivation (,). However, the exact mechanism underlyingthe thyroid hormone-induced synthesis of osteocalcin remains to beelucidated.