Description): The osteoblast is the bone-forming cell and there is a growing body of clinical evidence that functional defects of the osteoblast can be at the origin of osteoporosis. This observation underlines the importance of understanding the molecular mechanisms of osteoblast differentiation and function. To address this question, the investigators have cloned and characterized the first transcriptional activator of osteoblast differentiation termed Osf2/Cbfal. Osf2/Cbfal controls osteoblast differentiation during development but also the expression of several structural genes expressed in osteoblasts. The hypothesis is that Osf2/Cbfal is required in postnatal life to maintain the osteoblast phenotype. To test the multiple functions of Osf2/Cbfal during development and after birth, they propose: -to perform an extensive study of Osf2/Cbfal pattern of expression during development and after birth as well as a study of other molecular markers involved during skeletogenesis in wild-type and Cbfal-deficient mice; -to analyze the differentiation ability of Osf2/Cbfal in cell culture and in vivo; -to inhibit or abrogate Osf2/Cbfal function in differentiated osteoblasts in vivo; and -to overexpress Osf2/Cbfal in osteoblasts in vivo and determine if this overexpression leads to an increase in bone formation.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Research Project (R01)
Project #
5R01AR045548-03
Application #
6171155
Study Section
Special Emphasis Panel (ZHD1-RRG-K (06))
Program Officer
Sharrock, William J
Project Start
1998-04-01
Project End
2002-06-30
Budget Start
2000-04-01
Budget End
2002-06-30
Support Year
3
Fiscal Year
2000
Total Cost
$328,172
Indirect Cost
Name
Baylor College of Medicine
Department
Genetics
Type
Schools of Medicine
DUNS #
074615394
City
Houston
State
TX
Country
United States
Zip Code
77030
Mera, Paula; Laue, Kathrin; Wei, Jianwen et al. (2016) Osteocalcin is necessary and sufficient to maintain muscle mass in older mice. Mol Metab 5:1042-7
Mera, Paula; Laue, Kathrin; Ferron, Mathieu et al. (2016) Osteocalcin Signaling in Myofibers Is Necessary and Sufficient for Optimum Adaptation to Exercise. Cell Metab 23:1078-1092
Ferron, Mathieu; Lacombe, Julie; Germain, Amélie et al. (2015) GGCX and VKORC1 inhibit osteocalcin endocrine functions. J Cell Biol 208:761-76
Wei, Jianwen; Flaherty, Stephen; Karsenty, Gerard (2015) Searching for additional endocrine functions of the skeleton: genetic approaches and implications for therapeutics. Expert Rev Endocrinol Metab 10:413-424
Swanson, Christine M; Shea, Steven A; Stone, Katie L et al. (2015) Obstructive sleep apnea and metabolic bone disease: insights into the relationship between bone and sleep. J Bone Miner Res 30:199-211
Wei, Jianwen; Shimazu, Junko; Makinistoglu, Munevver P et al. (2015) Glucose Uptake and Runx2 Synergize to Orchestrate Osteoblast Differentiation and Bone Formation. Cell 161:1576-1591
Wei, Jianwen; Karsenty, Gerard (2015) An overview of the metabolic functions of osteocalcin. Rev Endocr Metab Disord 16:93-8
Wei, Jianwen; Hanna, Timothy; Suda, Nina et al. (2014) Osteocalcin promotes ?-cell proliferation during development and adulthood through Gprc6a. Diabetes 63:1021-31
Karsenty, Gerard; Oury, Franck (2014) Regulation of male fertility by the bone-derived hormone osteocalcin. Mol Cell Endocrinol 382:521-526
Obri, Arnaud; Makinistoglu, Munevver Parla; Zhang, Hong et al. (2014) HDAC4 integrates PTH and sympathetic signaling in osteoblasts. J Cell Biol 205:771-80

Showing the most recent 10 out of 36 publications