Bone regeneration is of enormous importance, particularly in the oral and craniofacial region. Trauma, including surgical removal of tumors in the oral and maxillofacial region, causes bone damage and injury. Congenital disorders may carry severe tissue defects that interfere with normal function and are often disfiguring. The ultimate therapeutic goal for these diseases is regeneration of the tissues to a normal or pre-disease state. Our long-range goal is to determine the cellular and molecular mechanisms involved in the regeneration of dental and craniofacial tissues and to further the development of products for skeletal regeneration and tissue engineering. The objectives of this application are to determine the source and potential of adult stem cells in tissue regeneration and to elucidate the roles of osterix (Osx), a critical osteogenic transcription factor, in the differentiation of bone- and dentin-forming cells. The central hypotheses to be tested are that marrow-derived cells are capable of regenerating oral craniofacial tissues and Osx stimulates the normal cascade of bone anabolic behavior. The rationale is based on the evidence that the conversion of marrow-derived non-differentiated mesenchymal stem cells into mature and functional osteo- and odonto-blasts is a crucial step in bone and dentin formation, as well as in regeneration.
Aim 1 : To determine the differentiation potential and histogenesis of bone marrow stromal cells (BMSCs) in oral craniofacial regeneration. Using a cell-based approach, the genetically labeled BMSCs will be introduced into oral, dental and craniofacial wounds and, for the first time, the cell differentiation, migration, and subsequent bone and dentin formation in a live animal will be documented.
Aim 2 : To determine, in vivo, the effects and mechanisms of Osx in promoting BMSC differentiation in bone regeneration and tissue engineering. Using a gene-therapy strategy, Osx will specifically target the bone- marrow and/or local-tissue derived cells, and for the first time, the effects of Osx promoting cell differentiation and enhancing osteogenesis and dentinogenesis will be determined in a novel transgenic model. Results derived from these studies in live animals will help identify new sources of cells, which are the most important element and most powerful engine for tissue engineering. These investigations will also provide novel and important insights into bone and tooth tissue formation using a gene-therapy approach, which will certainly benefit the patients who have tissue defects, damages and injuries in mouth as well as craniofacial regions. ? ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of Dental & Craniofacial Research (NIDCR)
Type
Research Project (R01)
Project #
1R01DE016710-01A2
Application #
7207038
Study Section
Musculoskeletal Tissue Engineering Study Section (MTE)
Program Officer
Lumelsky, Nadya L
Project Start
2007-04-15
Project End
2011-03-31
Budget Start
2007-04-15
Budget End
2008-03-31
Support Year
1
Fiscal Year
2007
Total Cost
$356,839
Indirect Cost
Name
Tufts University
Department
Dentistry
Type
Schools of Dentistry
DUNS #
039318308
City
Boston
State
MA
Country
United States
Zip Code
02111
Xuan, Dongying; Han, Qianqian; Tu, Qisheng et al. (2016) Epigenetic Modulation in Periodontitis: Interaction of Adiponectin and JMJD3-IRF4 Axis in Macrophages. J Cell Physiol 231:1090-6
Han, Qianqian; Yang, Pishan; Wu, Yuwei et al. (2015) Epigenetically Modified Bone Marrow Stromal Cells in Silk Scaffolds Promote Craniofacial Bone Repair and Wound Healing. Tissue Eng Part A 21:2156-65
Meng, S; Zhang, L; Tang, Y et al. (2014) BET Inhibitor JQ1 Blocks Inflammation and Bone Destruction. J Dent Res 93:657-62
Zhang, Lan; Meng, Shu; Tu, Qisheng et al. (2014) Adiponectin ameliorates experimental periodontitis in diet-induced obesity mice. PLoS One 9:e97824
Zhang, W; Zhu, C; Wu, Y et al. (2014) VEGF and BMP-2 promote bone regeneration by facilitating bone marrow stem cell homing and differentiation. Eur Cell Mater 27:1-11; discussion 11-2
Wu, Yuwei; Tu, Qisheng; Valverde, Paloma et al. (2014) Central adiponectin administration reveals new regulatory mechanisms of bone metabolism in mice. Am J Physiol Endocrinol Metab 306:E1418-30
Yan, S G; Zhang, J; Tu, Q et al. (2013) Transcription factor and bone marrow stromal cells in osseointegration of dental implants. Eur Cell Mater 26:263-70; discussion 270-1
Gong, Y; Bi, W; Cao, L et al. (2013) Association of CD14-260 polymorphisms, red-complex periodontopathogens and gingival crevicular fluid cytokine levels with cyclosporine A-induced gingival overgrowth in renal transplant patients. J Periodontal Res 48:203-12
Luo, En; Hu, Jing; Bao, Chongyun et al. (2012) Sustained release of adiponectin improves osteogenesis around hydroxyapatite implants by suppressing osteoclast activity in ovariectomized rabbits. Acta Biomater 8:734-43
Zhang, Wenjie; Wang, Xiuli; Wang, Shaoyi et al. (2011) The use of injectable sonication-induced silk hydrogel for VEGF(165) and BMP-2 delivery for elevation of the maxillary sinus floor. Biomaterials 32:9415-24

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