Bone Remodeling/Bone Sialoproteins

The main focuses of the Division of Oral Biology lab include:

  • Gene expression and regulation in bone formation and tooth development.
  • Stem cells and transcription factors in bone tissue engineering and regeneration.
  • Translational studies including bone metastasis of breast cancer cells, bisphosphonates associated osteonecrosis of the jaws and osseointegration of dental implants.

Bone sialoprotein (BSP) is a major non-collagenous protein in bone and other mineralized tissues. Our lab has demonstrated that that BSP is expressed during de novo bone formation and in initial stage of mineralization.

Using transgenic mouse model, we were the first in reporting the expression of rat BSP promoter in a tissue specific and developmentally regulated fashion. The transcriptional factor Cbfa1 is a “master gene” in osteogenenis. In Cbfa1 deficient mice there was no bone formation. We are currently investigating the regulation of Cbfa1 on BSP gene expression. In addition to a variety of in vitro studies we have also used a TVA (a chicken retroviral receptor) model to study the regulatory effect of Cbfa1 on BSP expression in vivo during deferent stages of tooth and bone development.

Using BSP as a unique marker and parameter, we have studied the cell differentiation in bone repair and regeneration. Calvarial and femoral bones as well as periodontal alveolar bone have been used in this tissue-engineering project in which both gene-therapy and cell-based in vivo methods have been applied. The migration, differentiation and function of bone marrow stem cells from BSP transgenic mice have been studied in periodontal regeneration. We have also first subcloned, sequenced and characterized hamster BSP gene and reported the BSP expression in cancer model.

It has recently been found that BSP is expressed in breast and prostate cancer cells that have a strong tendency to metastasize into bone tissues. We have started a series of investigations in determining the mechanisms of BSP gene expression in promoting bone metastasis of tumor cells. We have shown that BSP promotes tumor cell to penetrate blood vessels. Using an intracardiac injection of tumor cells in nude mice we have found that BSP gene over-expression in human breast cancer cells enhances the tumor metastasis and transfecion with antisense of BSP inhibits this effect.

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, histology, immunohistochemistry, luciferase assays, PCR, DNA and viral construction, cell and tissue cultures.