Researchers Find the Central Orchestrator in Bone and Tooth

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A group of scientists, Drs. Jin Zhang and Qisheng Tu et al from Chen lab, Tufts University, attended the Gordon Research Conference (GRC) “Bones and Teeth” from July 15 to 20, 2007 in Biddeford, Maine. Prestigious GRC represents one of the highest levels of research in the field. Through formal application and strict selection eligible attendees present their unpublished research data and exchange their research ideas in GRCs. Dr. Zhang and Dr. Tu presented an abstract entitled “Roles of SATB2 Overexpression in Regulating Tooth Development and Osteoblast Differentiation”.

      SATB2 gene has recently been proved to play pivotal roles in craniofacial development and osteoblast differentiation. Mouse embryos in which SATB2 expressions are genetically eliminated show multiple craniofacial defects including a shortening of the nasal and jaw bones, malformations of the hyoid bone, and a cleft palate. Using in situ hybridization of the mouse embryos, they demonstrated that SATB2 was highly expressed in the dental mesenchymal components of incisors but not in the epithelial components. Moreover, SATB2 was highly expressed in the developing palate and mandibular bone matrix, and the expression of SATB2 in the edges of developing palatine processes was strong when these two processes were growing towards each other. SATB2 was also found to be expressed in detal follicle cells of molar tooth germs at the root forming stage, which indicated that SATB2 plays an important role in root formation. The researchers also found that increased SATB2 expression in dental follicle cells and bone marrow stromal cells enhanced the expressing levels of bone matrix proteins, some osteogenic factors, and VEGFA, an important growth factor for angiogenesis during tissue regeneration. Drs. Zhang and Tu also reported that elevated SATB2 level in bone forming cells increased the migration rate of these cells, which indicated that SATB2 plays a role in promoting engraftment of pre-osteoblasts during wound regeneration.

      Craniofacial defects due to congenital disorders, trauma, infectious diseases, or surgical removal of cysts and tumors have devastating functional, esthetic, social and emotional impact on patients. An estimated 1,600,000 bone grafts are performed every year in US to regenerate bone, of which 6 percent (96,000) are craniomaxillofacial in nature. “The ultimate therapeutic goal for these diseases is regeneration of the tissues to a normal or pre-disease state,” said Dr. Tu, the team leader, “Thus tissue engineering and reconstruction are of enormous importance, particularly in the oral and craniofacial region. Such regeneration requires differentiation of reparative cells that produce appropriate amounts of extracellular matrix components, in a precise temporal and spatial manner to form specific types of hard and soft connective tissues. Our work opens up the exciting possibility that SATB2 may (1) serves as a platform for organizing the functions of osteogenic transcription factors, angiogenic growth factors, and bone matrix proteins; (2) acts as a morphogen on undifferentiated mesenchymal cells; (3) modulates gene activity directly and (4) assembles complexes with other DNA binding proteins to potentiate their activities.”

      These interesting findings of Dr. Zhang and Dr. Tu won them an “Outstanding Poster Award” from the 2007 Gordon Research Conference, a prestigious award for the best researches in the field. As indicated by Dr. Tu, SATB2 orchestrates the expressions of a group of osteogenic transcription factors and matrix proteins and thus plays a pivotal role in craniofacial development and osteoblastogenesis. Their studies strongly indicated that SATB2 stimulates and regulates stromal cells to regenerate vascularized periodontal tissues, and thus has a great potential in developing gene-therapy approaches to treat the dental patients.