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Published on 4/23/2019
Principal Investigator: Jake (Jinkun) Chen, DDS, Ph.D. Professor
DDS, Shanghai Second Medical University, 1982
M. Dent. Sci. and Oral Pathology Certificate, University of Connecticut, 1988
Ph.D., University of Toronto, Canada, 1992
Department of General Dentistry
Department of Anatomy and Cell BiologyDepartment of Anatomy & Cellular Biology Tufts University School of Medicine136 Harrison AvenueBoston, Massachusetts 02111
We have focused our efforts on gene expression and regulation of extracellular matrix proteins in bone development. Using transgenic mouse model we were the first in reporting the expression of bone sialoprotein (BSP) promoter in a tissue specific and developmentally regulated fashion. We have also, for this first time, established a unique and versatile TVA (a chicken retroviral receptor) model to study the effects of a variety of regulatory factors, including “master genes” Runx2/Cbfa1 and osterix (Osx) in vivo during deferent stages of bone development. We have recently identified the signal transduction pathway of BSP in osteoclast formation and bone resorption.
We are currently studying cell differentiation in bone regeneration and tissue engineering. We have used bone marrow stem cells to regenerate calvarial, femoral and periodontal alveolar bones in which both gene-therapy and cell-based approaches have been applied. Using specific transgenic models we are able to identify the migration, differentiation and fate of transplanted cells in tissue engineering in live animals.
We have first cloned, sequenced and characterized hamster BSP and osteopontin genes and reported their expression in carcinogensis. We have started a series of investigations in determining the effects and mechanisms of extracellular matrix proteins and growth factors in promoting bone metastasis of human breast cancer cells. In these experiments, intracardiac injection of tumor cells in nude mice, siRNA delivered by lentivira vectors, and DNA antisense strategies have been used.
The tools and methods we routinely employ in our lab include Northern, Southern, Western and in situ hybridizations, transgenic animal model, animal surgery and experimental pathology, tumorigenesis, histomorphometry, immunohistochemistry, luciferase assays, TVA viral receptor model , cell and tissue cultures, signal transduction pathway.
Selected Publications in 2008:
Zhang J, Zhu J, Valverde P, Li L, Pageau S, Tu Q, Nishimura R, Yoneda T, Yang P, Zheng W, Ma W, Chen J. Phenotypic analysis of Dlx5 overexpression in post-natal bone. J Dent Res 87:45-50, 2008.
Li S, Tu Q, Zhang J, Stein G, Lian J, Yang PS, Chen J. Systemically transplanted bone marrow stromal cells contributing to bone tissue regeneration. J Cell Physiol. 215:204-9, 2008.
Valverde P, Zhang J, Fix A, Zhu J, Ma W, Tu Q, Chen J. Overexpression of Bone Sialoprotein Leads to an Uncoupling of Bone Formation and Bone Resorption in Mice. J Bone Miner Res. 2008 Jul 2. [Epub ahead of print]
Tu Q, Zhang J, Paz J, Wade K, Yang P, Chen J. Haploinsufficiency of Runx2 results in bone formation decrease and different BSP expression pattern changes in two transgenic mouse models. J Cell Physiol. 217:40-7, 2008.
Zhao Y, Wang C, Li S, Song H, Wei F, Pan K, Zhu K, Yang P, Tu Q, Chen J. Expression of Osterix in mechanical stress-induced osteogenic differentiation of periodontal ligament cells in vitro. Eur J Oral Sci. 116(3):199-206, 2008.
Tu Q, Zhang J, Fix A, Brewer E, Li YP, Zhang ZY, Chen J. Targeted overexpression of BSP in osteoclasts promotes bone metastasis of breast cancer cells. J Cell Physiol. 2008 Aug 28. [Epub ahead of print]
Zhang J, Tu Q, Pageau S, Tang J and Chen J. Establishment of an Animal Model for Bisphosphonates-Associated ONJ to Investigate the Roles of Zoledronic Acid in Bone Healing and Osteoblast Functions. Submitted, 2008.
Xu B, Zhang J, Brewer E, Tu Q, Wieland M, Yu L and Chen J. Bone Marrow Stromal Cells and Osterix Contributing to Osseointegration of Dental Implants. Submitted, 2008.
Xu P, Zhang J, Liu H, Will L, Chapman RJ and Chen J. Evaluation of a Combined Prosth-Orthodontic Treatment for Maxillary Protrusion in Middle-Aged Adults. Submitted, 2008.
Zhang J, Tu Q and Chen J. Applications of Transgenics in studies of BSP. Submitted, 2008
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