Gene Symbol: Bglap2
Description: bone gamma-carboxyglutamate protein 2
Alias: BGP2, Bglap1, Bgp, Og2, mOC-B, osteocalcin-2, bone Gla protein 2, gamma-carboxyglutamic acid-containing protein 2, osteocalcin
Species: mouse
Products:     Bglap2

Top Publications

  1. Zhou G, Zheng Q, Engin F, Munivez E, Chen Y, Sebald E, et al. Dominance of SOX9 function over RUNX2 during skeletogenesis. Proc Natl Acad Sci U S A. 2006;103:19004-9 pubmed
    ..In summary, SOX9 is dominant over RUNX2 function in mesenchymal precursors that are destined for a chondrogenic lineage during endochondral ossification...
  2. Zelzer E, McLean W, Ng Y, Fukai N, Reginato A, Lovejoy S, et al. Skeletal defects in VEGF(120/120) mice reveal multiple roles for VEGF in skeletogenesis. Development. 2002;129:1893-904 pubmed
    ..We also describe new in vivo evidence for a possible role of VEGF in chondrocyte maturation, and document that VEGF has a direct role in regulating osteoblastic activity based on in vivo evidence and organ culture experiments. ..
  3. Komori T, Yagi H, Nomura S, Yamaguchi A, Sasaki K, Deguchi K, et al. Targeted disruption of Cbfa1 results in a complete lack of bone formation owing to maturational arrest of osteoblasts. Cell. 1997;89:755-64 pubmed
    ..Although immature osteoblasts, which expressed alkaline phophatase weakly but not Osteopontin and Osteocalcin, and a few immature osteoclasts appeared at the perichondrial region, neither vascular nor mesenchymal cell ..
  4. St Jacques B, Hammerschmidt M, McMahon A. Indian hedgehog signaling regulates proliferation and differentiation of chondrocytes and is essential for bone formation. Genes Dev. 1999;13:2072-86 pubmed
    ..Together, the results suggest a model in which Ihh coordinates diverse aspects of skeletal morphogenesis through PTHrP-dependent and independent processes. ..
  5. Hill T, Später D, Taketo M, Birchmeier W, Hartmann C. Canonical Wnt/beta-catenin signaling prevents osteoblasts from differentiating into chondrocytes. Dev Cell. 2005;8:727-38 pubmed
    ..Thus, canonical Wnt/beta-catenin signaling is essential for skeletal lineage differentiation, preventing transdifferentiation of osteoblastic cells into chondrocytes. ..
  6. Yang F, Tang W, So S, de Crombrugghe B, Zhang C. Sclerostin is a direct target of osteoblast-specific transcription factor osterix. Biochem Biophys Res Commun. 2010;400:684-8 pubmed publisher
    ..Taken together, these findings support our hypothesis that Sost is a direct target of Osx. This provides a new additional mechanism through which Osx inhibits Wnt signaling during bone formation. ..
  7. Satokata I, Ma L, Ohshima H, Bei M, Woo I, Nishizawa K, et al. Msx2 deficiency in mice causes pleiotropic defects in bone growth and ectodermal organ formation. Nat Genet. 2000;24:391-5 pubmed
    ..Our results provide a developmental basis for PFM and demonstrate that Msx2 is essential at multiple sites during organogenesis. ..
  8. Bialek P, Kern B, Yang X, Schrock M, Sosic D, Hong N, et al. A twist code determines the onset of osteoblast differentiation. Dev Cell. 2004;6:423-35 pubmed
    ..In vivo mutagenesis confirms the antiosteogenic function of the Twist box. Thus, relief of inhibition by Twist proteins is a mandatory event precluding osteoblast differentiation. ..
  9. Akiyama H, Lyons J, Mori Akiyama Y, Yang X, Zhang R, Zhang Z, et al. Interactions between Sox9 and beta-catenin control chondrocyte differentiation. Genes Dev. 2004;18:1072-87 pubmed
    ..Our results strongly suggest that chondrogenesis is controlled by interactions between Sox9 and the Wnt/beta-catenin signaling pathway. ..

More Information


  1. Ferron M, Hinoi E, Karsenty G, Ducy P. Osteocalcin differentially regulates beta cell and adipocyte gene expression and affects the development of metabolic diseases in wild-type mice. Proc Natl Acad Sci U S A. 2008;105:5266-70 pubmed publisher
    The osteoblast-specific secreted molecule osteocalcin behaves as a hormone regulating glucose metabolism and fat mass in two mutant mouse strains...
  2. Yoshizawa T, Handa Y, Uematsu Y, Takeda S, Sekine K, Yoshihara Y, et al. Mice lacking the vitamin D receptor exhibit impaired bone formation, uterine hypoplasia and growth retardation after weaning. Nat Genet. 1997;16:391-6 pubmed
    ..These defects, such as alopoecia and uterine hypoplasia, were not observed in vitamin D-deficient animals. The findings establish a critical role for VDR in growth, bone formation and female reproduction in the post-weaning stage. ..
  3. Nakashima K, Zhou X, Kunkel G, Zhang Z, Deng J, Behringer R, et al. The novel zinc finger-containing transcription factor osterix is required for osteoblast differentiation and bone formation. Cell. 2002;108:17-29 pubmed
    ..Thus, Osx acts downstream of Runx2/Cbfa1. Because Osx null preosteoblasts express typical chondrocyte marker genes, we propose that Runx2/Cbfa1-expressing preosteoblasts are still bipotential cells. ..
  4. Ferron M, Wei J, Yoshizawa T, Del Fattore A, Depinho R, Teti A, et al. Insulin signaling in osteoblasts integrates bone remodeling and energy metabolism. Cell. 2010;142:296-308 pubmed publisher
    ..expressing this receptor is the osteoblast, a bone-specific cell favoring glucose metabolism through a hormone, osteocalcin, that becomes active once uncarboxylated...
  5. Yang Y, Topol L, Lee H, Wu J. Wnt5a and Wnt5b exhibit distinct activities in coordinating chondrocyte proliferation and differentiation. Development. 2003;130:1003-15 pubmed
    ..Our data indicate that Wnt5a and Wnt5b control the pace of transitions between different chondrocyte zones. ..
  6. Jacob A, Smith C, Partanen J, Ornitz D. Fibroblast growth factor receptor 1 signaling in the osteo-chondrogenic cell lineage regulates sequential steps of osteoblast maturation. Dev Biol. 2006;296:315-28 pubmed
    ..These data demonstrate that signaling through FGFR1 in osteoblasts is necessary to maintain the balance between bone formation and remodeling through a direct effect on osteoblast maturation. ..
  7. Aghaloo T, Cowan C, Chou Y, Zhang X, Lee H, Miao S, et al. Nell-1-induced bone regeneration in calvarial defects. Am J Pathol. 2006;169:903-15 pubmed
    ..immunohistochemistry indicated that Nell-1 reduced osterix-producing cells and increased bone sialoprotein, osteocalcin, and BMP-7 expression...
  8. Hinoi E, Gao N, Jung D, Yadav V, Yoshizawa T, Myers M, et al. The sympathetic tone mediates leptin's inhibition of insulin secretion by modulating osteocalcin bioactivity. J Cell Biol. 2008;183:1235-42 pubmed publisher
    The osteoblast-secreted molecule osteocalcin favors insulin secretion, but how this function is regulated in vivo by extracellular signals is for now unknown...
  9. Akiyama H, Kim J, Nakashima K, Balmes G, Iwai N, Deng J, et al. Osteo-chondroprogenitor cells are derived from Sox9 expressing precursors. Proc Natl Acad Sci U S A. 2005;102:14665-70 pubmed
    ..Thus, our results strongly suggest that all osteo-chondroprogenitor cells, as well as progenitors in a variety of tissues, are derived from Sox9-expressing precursors during mouse embryogenesis. ..
  10. Smith N, Dong Y, Lian J, Pratap J, Kingsley P, Van Wijnen A, et al. Overlapping expression of Runx1(Cbfa2) and Runx2(Cbfa1) transcription factors supports cooperative induction of skeletal development. J Cell Physiol. 2005;203:133-43 pubmed
  11. Oury F, Ferron M, Huizhen W, Confavreux C, Xu L, LaCombe J, et al. Osteocalcin regulates murine and human fertility through a pancreas-bone-testis axis. J Clin Invest. 2013;123:2421-33 pubmed
    The osteoblast-derived hormone osteocalcin promotes testosterone biosynthesis in the mouse testis by binding to GPRC6A in Leydig cells...
  12. Colnot C, de la Fuente L, Huang S, Hu D, Lu C, St Jacques B, et al. Indian hedgehog synchronizes skeletal angiogenesis and perichondrial maturation with cartilage development. Development. 2005;132:1057-67 pubmed
  13. Joeng K, Long F. The Gli2 transcriptional activator is a crucial effector for Ihh signaling in osteoblast development and cartilage vascularization. Development. 2009;136:4177-85 pubmed publisher
    ..These results therefore provide direct genetic evidence that Gli2 and Gli3 collectively mediate all major aspects of Ihh function during endochondral skeletal development. ..
  14. Xiao G, Jiang D, Ge C, Zhao Z, Lai Y, Boules H, et al. Cooperative interactions between activating transcription factor 4 and Runx2/Cbfa1 stimulate osteoblast-specific osteocalcin gene expression. J Biol Chem. 2005;280:30689-96 pubmed
    ..In this study, we determined the molecular mechanisms through which ATF4 activates the mouse osteocalcin (Ocn) gene 2 (mOG2) expression and mOG2 promoter activity...
  15. Ducy P, Desbois C, Boyce B, Pinero G, Story B, Dunstan C, et al. Increased bone formation in osteocalcin-deficient mice. Nature. 1996;382:448-52 pubmed
    ..To investigate the role of osteocalcin, the most abundant osteoblast-specific non-collagenous protein, we have generated osteocalcin-deficient mice...
  16. Acampora D, Merlo G, Paleari L, Zerega B, Postiglione M, Mantero S, et al. Craniofacial, vestibular and bone defects in mice lacking the Distal-less-related gene Dlx5. Development. 1999;126:3795-809 pubmed
    ..The defects observed in Dlx5-/- mutant animals suggest multiple and independent roles of this gene in the patterning of the branchial arches, in the morphogenesis of the vestibular organ and in osteoblast differentiation. ..
  17. Oury F, Sumara G, Sumara O, Ferron M, Chang H, Smith C, et al. Endocrine regulation of male fertility by the skeleton. Cell. 2011;144:796-809 pubmed publisher
    ..Analyses of cell-specific loss- and gain-of-function models reveal that the osteoblast-derived hormone osteocalcin performs this endocrine function...
  18. Lee N, Sowa H, Hinoi E, Ferron M, Ahn J, Confavreux C, et al. Endocrine regulation of energy metabolism by the skeleton. Cell. 2007;130:456-69 pubmed
    ..In contrast, mice lacking the osteoblast-secreted molecule osteocalcin display decreased beta-cell proliferation, glucose intolerance, and insulin resistance...
  19. Takeda S, Bonnamy J, Owen M, Ducy P, Karsenty G. Continuous expression of Cbfa1 in nonhypertrophic chondrocytes uncovers its ability to induce hypertrophic chondrocyte differentiation and partially rescues Cbfa1-deficient mice. Genes Dev. 2001;15:467-81 pubmed
    ..These results identify Cbfa1 as a hypertrophic chondrocyte differentiation factor and provide a genetic argument for a common regulation of osteoblast and chondrocyte differentiation mediated by Cbfa1. ..
  20. Holmes G, Bromage T, Basilico C. The Sox2 high mobility group transcription factor inhibits mature osteoblast function in transgenic mice. Bone. 2011;49:653-61 pubmed publisher
    ..Our results position Sox2 as a negative regulator of osteoblast maturation in vivo. ..
  21. Han M, Yang X, Lee J, Allan C, Muneoka K. Development and regeneration of the neonatal digit tip in mice. Dev Biol. 2008;315:125-35 pubmed publisher
    ..These clinical and experimental findings expand on previously published observations and initiate a molecular assessment of a mammalian regeneration model. ..
  22. Yu K, Xu J, Liu Z, Sosic D, Shao J, Olson E, et al. Conditional inactivation of FGF receptor 2 reveals an essential role for FGF signaling in the regulation of osteoblast function and bone growth. Development. 2003;130:3063-74 pubmed
    ..Although differentiation of the osteoblast lineage was not disturbed, the proliferation of osteoprogenitors and the anabolic function of mature osteoblasts were severely affected. ..
  23. Holmes G, Rothschild G, Roy U, Deng C, Mansukhani A, Basilico C. Early onset of craniosynostosis in an Apert mouse model reveals critical features of this pathology. Dev Biol. 2009;328:273-84 pubmed publisher
  24. Sommer B, Bickel M, Hofstetter W, Wetterwald A. Expression of matrix proteins during the development of mineralized tissues. Bone. 1996;19:371-80 pubmed
    ..the expression of the enamel protein amelogenin and of the bone matrix proteins osteopontin, bone sialoprotein, osteocalcin, and osteonectin was investigated by in situ hybridization...
  25. Aqeilan R, Hassan M, de Bruin A, Hagan J, Volinia S, Palumbo T, et al. The WWOX tumor suppressor is essential for postnatal survival and normal bone metabolism. J Biol Chem. 2008;283:21629-39 pubmed publisher
    ..physically associates with RUNX2, the principal transcriptional regulator of osteoblast differentiation, and on osteocalcin chromatin. We show WWOX functionally suppresses RUNX2 transactivation ability in osteoblasts...
  26. Sowa H. [Regulation of energy metabolism by bone]. Clin Calcium. 2008;18:644-9 pubmed publisher
    ..Gerard Karsenty and his colleagues studied energy metabolism in the mice lacking Osteocalcin, an osteoblast-specific gene...
  27. Zhang C, Tang W, Li Y, Yang F, Dowd D, MacDonald P. Osteoblast-specific transcription factor Osterix increases vitamin D receptor gene expression in osteoblasts. PLoS ONE. 2011;6:e26504 pubmed publisher
    ..They further provide new insight into potential mechanisms and pathways that Osx controls in osteoblasts and during the process of osteoblastic cell differentiation. ..
  28. Wang W, Lian N, Ma Y, Li L, Gallant R, Elefteriou F, et al. Chondrocytic Atf4 regulates osteoblast differentiation and function via Ihh. Development. 2012;139:601-11 pubmed publisher
    Atf4 is a leucine zipper-containing transcription factor that activates osteocalcin (Ocn) in osteoblasts and indian hedgehog (Ihh) in chondrocytes...
  29. Shin C, Jeon M, Yang J, Her S, Kim D, Kim S, et al. CCAAT/enhancer-binding protein delta activates the Runx2-mediated transcription of mouse osteocalcin II promoter. J Mol Endocrinol. 2006;36:531-46 pubmed
    ..roles of C/EBPs in osteoblasts are largely unknown, both C/EBPbeta and -delta have been shown to enhance rat osteocalcin promoter activity through the synergistic activation of Runx2 at the C/EBP element...
  30. Schroeder T, Kahler R, Li X, Westendorf J. Histone deacetylase 3 interacts with runx2 to repress the osteocalcin promoter and regulate osteoblast differentiation. J Biol Chem. 2004;279:41998-2007 pubmed
    ..In transient transfection assays, HDAC3 repressed Runx2-mediated activation of the osteocalcin promoter. HDAC inhibitors and HDAC3-specific short hairpin RNAs reversed this repression...
  31. Gori F, Friedman L, Demay M. Wdr5, a WD-40 protein, regulates osteoblast differentiation during embryonic bone development. Dev Biol. 2006;295:498-506 pubmed
    ..Overall, our findings suggest that Wdr5 accelerates osteoblast differentiation in association with activation of the canonical Wnt pathway. ..
  32. Maeda K, Enomoto A, Hara A, Asai N, Kobayashi T, Horinouchi A, et al. Identification of Meflin as a Potential Marker for Mesenchymal Stromal Cells. Sci Rep. 2016;6:22288 pubmed publisher
    ..These preliminary data suggest that Meflin is a potential marker for cultured MSCs and their source cells in vivo. ..
  33. Hung I, Yu K, Lavine K, Ornitz D. FGF9 regulates early hypertrophic chondrocyte differentiation and skeletal vascularization in the developing stylopod. Dev Biol. 2007;307:300-13 pubmed
    ..In developing stylopod elements, FGF9 promotes chondrocyte hypertrophy at early stages and regulates vascularization of the growth plate and osteogenesis at later stages of skeletal development. ..
  34. Kavukcuoglu N, Patterson Buckendahl P, Mann A. Effect of osteocalcin deficiency on the nanomechanics and chemistry of mouse bones. J Mech Behav Biomed Mater. 2009;2:348-54 pubmed publisher
    ..The deterioration is typically accompanied by changes in the non-collagenous proteins in the bone. Osteocalcin (OC) is the most abundant noncollageneous bone matrix protein and it is believed to play a role in bone ..
  35. Varga F, Rumpler M, Spitzer S, Karlic H, Klaushofer K. Osteocalcin attenuates T3- and increases vitamin D3-induced expression of MMP-13 in mouse osteoblasts. Endocr J. 2009;56:441-50 pubmed
    b>Osteocalcin (OCN), the most abundant non-collagenous protein of the bone matrix, whose function is not fully understood, was recently suggested to act as endocrine factor regulating energy metabolism...
  36. Zhou Z, Shung C, Ota S, Akiyama H, Keene D, Hurlin P. Sequential and coordinated actions of c-Myc and N-Myc control appendicular skeletal development. PLoS ONE. 2011;6:e18795 pubmed publisher
    ..Our results show that N-Myc and c-Myc act sequentially during limb development to coordinate the expansion of key progenitor populations responsible for forming the limb skeleton. ..
  37. Kohn A, Dong Y, Mirando A, Jesse A, Honjo T, Zuscik M, et al. Cartilage-specific RBPj?-dependent and -independent Notch signals regulate cartilage and bone development. Development. 2012;139:1198-212 pubmed publisher
    ..Finally, cartilage-specific RBPj?-independent Notch signaling likely regulates Ihh responsiveness during cartilage and bone development. ..
  38. Rached M, Kode A, Silva B, Jung D, Gray S, Ong H, et al. FoxO1 expression in osteoblasts regulates glucose homeostasis through regulation of osteocalcin in mice. J Clin Invest. 2010;120:357-68 pubmed publisher
    Osteoblasts have recently been found to play a role in regulating glucose metabolism through secretion of osteocalcin. It is unknown, however, how this osteoblast function is regulated transcriptionally...
  39. Wei J, Ferron M, Clarke C, Hannun Y, Jiang H, Blaner W, et al. Bone-specific insulin resistance disrupts whole-body glucose homeostasis via decreased osteocalcin activation. J Clin Invest. 2014;124:1-13 pubmed publisher
    ..Insulin resistance in osteoblasts led to a decrease in circulating levels of the active form of osteocalcin, thereby decreasing insulin sensitivity in skeletal muscle...
  40. Zhou Z, Ota S, Deng C, Akiyama H, Hurlin P. Mutant activated FGFR3 impairs endochondral bone growth by preventing SOX9 downregulation in differentiating chondrocytes. Hum Mol Genet. 2015;24:1764-73 pubmed publisher
    ..These findings suggest that a proliferation-independent and SOX9-dependent differentiation block is a key driving mechanism responsible for poor endochondral bone growth in achondroplasia disorders caused by mutations in FGFR3. ..
  41. Morello R, Bertin T, Schlaubitz S, Shaw C, Kakuru S, Munivez E, et al. Brachy-syndactyly caused by loss of Sfrp2 function. J Cell Physiol. 2008;217:127-37 pubmed publisher
  42. Kovacs C, Chafe L, Fudge N, Friel J, Manley N. PTH regulates fetal blood calcium and skeletal mineralization independently of PTHrP. Endocrinology. 2001;142:4983-93 pubmed
  43. Shin H, Divieti P, Sims N, Kobayashi T, Miao D, Karaplis A, et al. Gp130-mediated signaling is necessary for normal osteoblastic function in vivo and in vitro. Endocrinology. 2004;145:1376-85 pubmed
    ..These studies demonstrate the importance of gp130 signaling for osteoblast function and calcium homeostasis. ..
  44. Park M, Shin H, Choi J, Nam S, Kim Y, Kim H, et al. Differential expression patterns of Runx2 isoforms in cranial suture morphogenesis. J Bone Miner Res. 2001;16:885-92 pubmed
    ..expressed in the osteogenic fronts, as well as in developing parietal bones, where osteopontin (OP) and osteocalcin (OC) also were expressed...
  45. Maes C, Goossens S, Bartunkova S, Drogat B, Coenegrachts L, Stockmans I, et al. Increased skeletal VEGF enhances beta-catenin activity and results in excessively ossified bones. EMBO J. 2010;29:424-41 pubmed publisher
    ..Moreover, the finding that VEGF can modulate beta-catenin activity may have widespread physiological and clinical ramifications. ..
  46. Holm E, Aubin J, Hunter G, Beier F, Goldberg H. Loss of bone sialoprotein leads to impaired endochondral bone development and mineralization. Bone. 2015;71:145-54 pubmed publisher
    ..These results suggest that BSP is an important and multifaceted protein that regulates both chondrocyte proliferation and apoptosis as well as transition from cartilage to bone during development of endochondral bone. ..
  47. Wei J, Shimazu J, Makinistoglu M, Maurizi A, Kajimura D, Zong H, et al. Glucose Uptake and Runx2 Synergize to Orchestrate Osteoblast Differentiation and Bone Formation. Cell. 2015;161:1576-1591 pubmed publisher
    ..These results reveal an unexpected intricacy between bone and glucose metabolism. ..
  48. Robledo R, Rajan L, Li X, Lufkin T. The Dlx5 and Dlx6 homeobox genes are essential for craniofacial, axial, and appendicular skeletal development. Genes Dev. 2002;16:1089-101 pubmed
    ..Furthermore, spatiotemporal-specific transgenic overexpression of Dlx5, in the apical ectodermal ridge of Dlx5/6 null mice can fully rescue Dlx/Dll function in limb outgrowth. ..
  49. Oury F, Khrimian L, Denny C, Gardin A, Chamouni A, Goeden N, et al. Maternal and offspring pools of osteocalcin influence brain development and functions. Cell. 2013;155:228-41 pubmed publisher
    ..We show here that the osteoblast-derived hormone osteocalcin crosses the blood-brain barrier, binds to neurons of the brainstem, midbrain, and hippocampus, enhances the ..
  50. Choo M, Yeo H, Zayzafoon M. NFATc1 mediates HDAC-dependent transcriptional repression of osteocalcin expression during osteoblast differentiation. Bone. 2009;45:579-89 pubmed publisher a decrease in gene expression of early and late markers of osteoblast differentiation such as osterix and osteocalcin, respectively...
  51. Govindarajan V, Overbeek P. FGF9 can induce endochondral ossification in cranial mesenchyme. BMC Dev Biol. 2006;6:7 pubmed
    ..These changes are accompanied by upregulation of Sox9, Ihh, Col2a1, Col10a1 and downregulation of CbfaI and Osteocalcin. Fate mapping studies show that the cranial mesenchymal cells in the parietal region that show a switch in cell ..
  52. Kanamoto T, Mizuhashi K, Terada K, Minami T, Yoshikawa H, Furukawa T. Isolation and characterization of a novel plasma membrane protein, osteoblast induction factor (obif), associated with osteoblast differentiation. BMC Dev Biol. 2009;9:70 pubmed publisher
    ..Our results suggest that obif plays a role in osteoblastic differentiation by acting as a ligand. ..
  53. Yang T, Moore M, He F. Pten regulates neural crest proliferation and differentiation during mouse craniofacial development. Dev Dyn. 2018;247:304-314 pubmed publisher
    ..Our data further indicate that Pten acts via modulating PI3K/Akt activity during these processes. Developmental Dynamics 247:304-314, 2018. © 2017 Wiley Periodicals, Inc. ..
  54. Al Rifai O, Chow J, LaCombe J, Julien C, Faubert D, Susan Resiga D, et al. Proprotein convertase furin regulates osteocalcin and bone endocrine function. J Clin Invest. 2017;127:4104-4117 pubmed publisher
    b>Osteocalcin (OCN) is an osteoblast-derived hormone that increases energy expenditure, insulin sensitivity, insulin secretion, and glucose tolerance...
  55. Ohbayashi N, Shibayama M, Kurotaki Y, Imanishi M, Fujimori T, Itoh N, et al. FGF18 is required for normal cell proliferation and differentiation during osteogenesis and chondrogenesis. Genes Dev. 2002;16:870-9 pubmed
    ..Conversely, chondrocyte proliferation and the number of differentiated chondrocytes are increased. Therefore, FGF18 appears to regulate cell proliferation and differentiation positively in osteogenesis and negatively in chondrogenesis. ..
  56. Soegiarto D, Kiachopoulos S, Schipani E, Juppner H, Erben R, Lanske B. Partial rescue of PTH/PTHrP receptor knockout mice by targeted expression of the Jansen transgene. Endocrinology. 2001;142:5303-10 pubmed
    ..These findings suggested that factors other than impaired gas exchange due to an abnormal rib cage contribute to the early death of PPR(-/-) mice. ..
  57. Fen J, Zhang J, Dallas S, Lu Y, Chen S, Tan X, et al. Dentin matrix protein 1, a target molecule for Cbfa1 in bone, is a unique bone marker gene. J Bone Miner Res. 2002;17:1822-31 pubmed
    ..forced expression of Dmp1 under the control of Cbfa1 and gel shift data indicated the presence of a functional osteocalcin-specific element (OSE)-2 response element in the Dmp1 proximal promoter region...
  58. Luo J, Zhou W, Zhou X, Li D, Weng J, Yi Z, et al. Regulation of bone formation and remodeling by G-protein-coupled receptor 48. Development. 2009;136:2747-56 pubmed publisher
    ..we show that Gpr48 significantly downregulates the expression levels of Atf4 target genes/proteins, such as osteocalcin (Ocn; Bglap2), bone sialoprotein (Bsp; Ibsp) and collagen...
  59. Arnold M, Kim Y, Czubryt M, Phan D, McAnally J, Qi X, et al. MEF2C transcription factor controls chondrocyte hypertrophy and bone development. Dev Cell. 2007;12:377-89 pubmed
    ..These findings reveal unexpected commonalities in the mechanisms governing muscle, cardiovascular, and bone development with respect to their regulation by MEF2 and class II HDACs. ..
  60. Maes C, Carmeliet P, Moermans K, Stockmans I, Smets N, Collen D, et al. Impaired angiogenesis and endochondral bone formation in mice lacking the vascular endothelial growth factor isoforms VEGF164 and VEGF188. Mech Dev. 2002;111:61-73 pubmed
  61. Qin X, Jiang Q, Matsuo Y, Kawane T, Komori H, Moriishi T, et al. Cbfb regulates bone development by stabilizing Runx family proteins. J Bone Miner Res. 2015;30:706-14 pubmed publisher
    ..of chondrocytes and osteoblasts were severely inhibited in vitro, and the reporter activities of Ihh, Col10a1, and Bglap2 promoter constructs were reduced in Cbfb(fl/fl/Cre) chondrocytes or osteoblasts...
  62. Miclea R, Karperien M, Bosch C, van der Horst G, van der Valk M, Kobayashi T, et al. Adenomatous polyposis coli-mediated control of beta-catenin is essential for both chondrogenic and osteogenic differentiation of skeletal precursors. BMC Dev Biol. 2009;9:26 pubmed publisher
    ..Our data indicate that a tight Apc-mediated control of beta-catenin levels is essential for differentiation of skeletal precursors as well as for the maintenance of a chondrocytic phenotype in a spatio-temporal regulated manner. ..
  63. Shimazu J, Wei J, Karsenty G. Smurf1 Inhibits Osteoblast Differentiation, Bone Formation, and Glucose Homeostasis through Serine 148. Cell Rep. 2016;15:27-35 pubmed publisher
    ..mice, an increase in insulin signaling in osteoblasts that triggers a rise in the circulating levels of osteocalcin, a hormone that favors insulin secretion...
  64. Levi G, Topilko P, Schneider Maunoury S, Lasagna M, Mantero S, Cancedda R, et al. Defective bone formation in Krox-20 mutant mice. Development. 1996;122:113-20 pubmed
  65. Lei R, Zhang K, Wei Y, Chen M, Weinstein L, Hong Y, et al. G-Protein α-Subunit Gsα Is Required for Craniofacial Morphogenesis. PLoS ONE. 2016;11:e0147535 pubmed publisher
    ..Taken together, our study suggests that Gsα is required for neural crest cells-derived craniofacial development. ..
  66. Wei J, Hanna T, Suda N, Karsenty G, Ducy P. Osteocalcin promotes ?-cell proliferation during development and adulthood through Gprc6a. Diabetes. 2014;63:1021-31 pubmed publisher
    ..Here we show that osteocalcin, a bone-derived hormone, regulates ?-cell replication in a cyclin D1-dependent manner by signaling through the ..
  67. Doi M, Nagano A, Nakamura Y. Molecular cloning and characterization of a novel gene, EMILIN-5, and its possible involvement in skeletal development. Biochem Biophys Res Commun. 2004;313:888-93 pubmed
    ..5 days post-coitus revealed relatively high levels of EMILIN-5 protein in perichondrium cells of developing limbs. Our findings suggest that the EMILIN-5 gene plays an important role in skeletal development. ..
  68. Zhang C, Dai H, de Crombrugghe B. Characterization of Dkk1 gene regulation by the osteoblast-specific transcription factor Osx. Biochem Biophys Res Commun. 2012;420:782-6 pubmed publisher
    ..Taken together, these findings support our hypothesis that Dkk1 is a direct target of Osx. ..
  69. Soung D, Dong Y, Wang Y, Zuscik M, Schwarz E, O Keefe R, et al. Runx3/AML2/Cbfa3 regulates early and late chondrocyte differentiation. J Bone Miner Res. 2007;22:1260-70 pubmed
    ..Furthermore, Runx3 expression remains high during later stages of embryonic development when the levels of osteocalcin are maximal...
  70. Takarada T, Yoneda Y. Transactivation by Runt related factor-2 of matrix metalloproteinase-13 in astrocytes. Neurosci Lett. 2009;451:99-104 pubmed publisher
    ..and their targets such as osteopontin (OPN) and matrix metalloproteinase-13 (MMP13), but not for collagen-I or osteocalcin. In pluripotent P19 progenitor cells, Runx2 mRNA expression was drastically increased along with mRNA ..
  71. Desbois C, Hogue D, Karsenty G. The mouse osteocalcin gene cluster contains three genes with two separate spatial and temporal patterns of expression. J Biol Chem. 1994;269:1183-90 pubmed
    b>Osteocalcin is the most abundant noncollagenous protein of bone. Here we report that the mouse genome contains an osteocalcin cluster composed of three genes arranged within a 23-kilobase span of genomic DNA...
  72. Eitzinger N, Surmann Schmitt C, Bösl M, Schett G, Engelke K, Hess A, et al. Ucma is not necessary for normal development of the mouse skeleton. Bone. 2012;50:670-80 pubmed publisher
  73. Ideno H, Takanabe R, Shimada A, Imaizumi K, Araki R, Abe M, et al. Protein related to DAN and cerberus (PRDC) inhibits osteoblastic differentiation and its suppression promotes osteogenesis in vitro. Exp Cell Res. 2009;315:474-84 pubmed publisher
    ..PRDC is accordingly identified as a potential novel therapeutic target for the regulation of bone formation. ..
  74. Rahman S, Oberdorf A, Montecino M, Tanhauser S, Lian J, Stein G, et al. Multiple copies of the bone-specific osteocalcin gene in mouse and rat. Endocrinology. 1993;133:3050-3 pubmed
    The osteocalcin (OC) gene was initially described as a single copy gene encoding the bone specific vitamin K dependent and vitamin D regulated protein. We report here the presence of multiple copies of the gene in mouse and rat...
  75. Wiig H, Schröder A, Neuhofer W, Jantsch J, Kopp C, Karlsen T, et al. Immune cells control skin lymphatic electrolyte homeostasis and blood pressure. J Clin Invest. 2013;123:2803-15 pubmed publisher
  76. Elefteriou F, Benson M, Sowa H, Starbuck M, Liu X, Ron D, et al. ATF4 mediation of NF1 functions in osteoblast reveals a nutritional basis for congenital skeletal dysplasiae. Cell Metab. 2006;4:441-51 pubmed
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