Abstract

Osteoclast differentiation is normally assumed to be achieved through the differentiation of cells via a monocyte/macrophage differentiation pathway. The Pax5 deficient mouse strain accumulates a progenitor cell population that has properties suggestive of a proB cell phenotype. Treatment with RANKL and M-CSF results in differentiation of osteoclasts from bone marrow as well as spleen. An examination of bone from Pax5 deficient mice has revealed severe osteopenic phenotypic. This Proposal will definitively characterize the progenitors in bone marrow and spleen that can differentiate into osteoclasts. The bone marrow will be fractionated into distinct cell populations based on expression of cell surface markers and each population will be assessed for its capacity to differentiate into osteoclasts. Attempts will be made to immortalize ell clones that retain the capacity to differentiate in response to RANKL and M-CSF. Such cell lines could be used to dissect the signaling pathways for osteoclast differentiation characterize mechanisms of cell fusion into osteoclasts and identify and study the roles of additional genes that contribute to the differentiation process.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Center Core Grants (P30)
Project #
5P30AR046032-04
Application #
6587716
Study Section
Special Emphasis Panel (ZAR1)
Project Start
2002-04-01
Project End
2004-03-31
Budget Start
Budget End
Support Year
4
Fiscal Year
2002
Total Cost
Indirect Cost

  Institution

Name
Yale University
Department
Type
DUNS #
082359691
City
New Haven
State
CT
Country
United States
Zip Code
06520

  Publications

Zhu, Meiling; Sun, Ben-Hua; Saar, Katarzyna et al. (2016) Deletion of Rac in Mature Osteoclasts Causes Osteopetrosis, an Age-Dependent Change in Osteoclast Number, and a Reduced Number of Osteoblasts In Vivo. J Bone Miner Res 31:864-73
Belinsky, Glenn S; Sreekumar, Bharath; Andrejecsk, Jillian W et al. (2016) Pigment epithelium-derived factor restoration increases bone mass and improves bone plasticity in a model of osteogenesis imperfecta type VI via Wnt3a blockade. FASEB J 30:2837-48
Kim, Jae Geun; Sun, Ben-Hua; Dietrich, Marcelo O et al. (2015) AgRP Neurons Regulate Bone Mass. Cell Rep 13:8-14
Protiva, Petr; Gong, Jingjing; Sreekumar, Bharath et al. (2015) Pigment Epithelium-Derived Factor (PEDF) Inhibits Wnt/?-catenin Signaling in the Liver. Cell Mol Gastroenterol Hepatol 1:535-549.e14
Ardeshirpour, Laleh; Dumitru, Cristina; Dann, Pamela et al. (2015) OPG Treatment Prevents Bone Loss During Lactation But Does Not Affect Milk Production or Maternal Calcium Metabolism. Endocrinology 156:2762-73
Meijome, Tomas E; Hooker, R Adam; Cheng, Ying-Hua et al. (2015) GATA-1 deficiency rescues trabecular but not cortical bone in OPG deficient mice. J Cell Physiol 230:783-90
Wang, Meina; Nasiri, Ali R; Broadus, Arthur E et al. (2015) Periosteal PTHrP Regulates Cortical Bone Remodeling During Fracture Healing. Bone 81:104-111
Fretz, Jackie A; Nelson, Tracy; Velazquez, Heino et al. (2014) Early B-cell factor 1 is an essential transcription factor for postnatal glomerular maturation. Kidney Int 85:1091-102
Wang, Meina; VanHouten, Joshua N; Nasiri, Ali R et al. (2014) Periosteal PTHrP regulates cortical bone modeling during linear growth in mice. J Anat 225:71-82
Scheller, Erica L; Troiano, Nancy; Vanhoutan, Joshua N et al. (2014) Use of osmium tetroxide staining with microcomputerized tomography to visualize and quantify bone marrow adipose tissue in vivo. Methods Enzymol 537:123-39

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