This is a competitive renewal of The University of Alabama at Birmingham Core Center for Basic Skeletal Research (UAB CCBSR), Director: Jay M. McDonald, MD. The DAB CCBSR was founded to stimulate innovative, interdisciplinary approaches to the identification and characterization of the key mechanisms underlying bone loss and regeneration and the systemic and local factors that regulate these processes. The research base brings together 33 investigators with expertise in regulation of bone cell differentiation and function; cell-cell and cell-matrix interactions; and growth factor and hormonal regulation of bone cells and investigators with expertise in osteoporosis, periodontal disease, rheumatoid arthritis, bioengineering, and gene therapy. Progress during the first phase of funding (4 years) has been extraordinary: the funding base has increased to $12,654,831 in annual direct extramural bone-related funding; the CCBSR has supported over 250 bone-related publications; and a dynamic, collaborative research environment has been established. This progress can be attributed directly to the P30 funding: (1) the two research cores have supported 76 investigators; many having used both Cores, resulting in over 100 publications to date; and (2) the P&F program has supported 5 investigators who have obtained independent funding. This has facilitated recruitment of 7 new investigators in basic bone biology to UAB; a commitment of 43,000 net sq. ft. of new and renovated research space; and a multidisciplinary institutional commitment to hire 16 new bone biologists to UAB in the next four years. The infrastructure and Enrichment Programs of the Administrative Core have proven essential to the stimulation of innovative research targeting complex, multifactorial bone diseases, and have led to the rapid formation of new collaborative efforts as the research unfolds. The research cores, which are essential to the success of this dynamic program, include a: 1) Human Bone Cell Production Core providing human osteoclasts and osteoblasts and key reagents for molecular experimentation; 2) Histomorphometry and Molecular Analyses Core providing state-of-the-art histological, histomorphometric and highly sensitive cellular and tissue molecular probe techniques; and 3) Small Animal Bone Phenotyping Core providing comprehensive bone phenotyping by DEXA and micro CT. Three P&F studies have been competitively selected from 10 submissions: NFAT negatively regulates osteoblast differentiation and bone formation, M. Zayzafoon, MD, PhD; Role of hypoxia in bone formation, S. Gilbert, MD; and Mechanisms of oral bacteria-mediated bone resorption via toll-like receptors, H. Wu, PhD. The CCBSR has the potential to rapidly and significantly impact the prevention and treatment of osteoporosis and related bone diseases, as well as the development of more effective hard tissue implants through the basic and translational research necessary for the development of innovative therapeutic strategies.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Center Core Grants (P30)
Project #
5P30AR046031-08
Application #
7432614
Study Section
Special Emphasis Panel (ZAR1-YZW-H (O2))
Program Officer
Sharrock, William J
Project Start
2001-05-01
Project End
2011-05-31
Budget Start
2008-06-01
Budget End
2009-05-31
Support Year
8
Fiscal Year
2008
Total Cost
$565,122
Indirect Cost
Name
University of Alabama Birmingham
Department
Pathology
Type
Schools of Medicine
DUNS #
063690705
City
Birmingham
State
AL
Country
United States
Zip Code
35294
Chen, Wei; Zhu, Guochun; Tang, Jun et al. (2018) C/ebp? controls osteoclast terminal differentiation, activation, function, and postnatal bone homeostasis through direct regulation of Nfatc1. J Pathol 244:271-282
Chen, Wei; Zhu, Guochun; Jules, Joel et al. (2018) Monocyte-Specific Knockout of C/ebp? Results in Osteopetrosis Phenotype, Blocks Bone Loss in Ovariectomized Mice, and Reveals an Important Function of C/ebp? in Osteoclast Differentiation and Function. J Bone Miner Res 33:691-703
Jules, Joel; Chen, Wei; Feng, Xu et al. (2018) C/EBP? transcription factor is regulated by the RANK cytoplasmic 535IVVY538 motif and stimulates osteoclastogenesis more strongly than c-Fos. J Biol Chem 293:1480-1492
Wu, Mengrui; Wang, Yiping; Shao, Jian-Zhong et al. (2017) Cbf? governs osteoblast-adipocyte lineage commitment through enhancing ?-catenin signaling and suppressing adipogenesis gene expression. Proc Natl Acad Sci U S A 114:10119-10124
Cai, Xiaofeng; Xing, Junjie; Long, Courtney L et al. (2017) DOK3 Modulates Bone Remodeling by Negatively Regulating Osteoclastogenesis and Positively Regulating Osteoblastogenesis. J Bone Miner Res 32:2207-2218
Jules, Joel; Chen, Wei; Feng, Xu et al. (2016) CCAAT/Enhancer-binding Protein ? (C/EBP?) Is Important for Osteoclast Differentiation and Activity. J Biol Chem 291:16390-403
Levy, Seth; Feduska, Joseph M; Sawant, Anandi et al. (2016) Immature myeloid cells are critical for enhancing bone fracture healing through angiogenic cascade. Bone 93:113-124
Higgs, Jerome T; Jarboe, John S; Lee, Joo Hyoung et al. (2015) Variants of Osteoprotegerin Lacking TRAIL Binding for Therapeutic Bone Remodeling in Osteolytic Malignancies. Mol Cancer Res 13:819-27
Li, Sheng; Hao, Liang; Wang, Lin et al. (2015) Targeting Atp6v1c1 Prevents Inflammation and Bone Erosion Caused by Periodontitis and Reveals Its Critical Function in Osteoimmunology. PLoS One 10:e0134903
Deshane, Jessy S; Redden, David T; Zeng, Meiqin et al. (2015) Subsets of airway myeloid-derived regulatory cells distinguish mild asthma from chronic obstructive pulmonary disease. J Allergy Clin Immunol 135:413-424.e15

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