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ABSTRACT

Advancing our understanding of osteoblast biology and differentiation is critical to elucidate the pathological mechanisms responsible for skeletal diseases such as osteoporosis. Histology and histomorphometry, the classical methods to study osteoblast biology, identify osteoblasts based on their location and morphology and ability to mineralize matrix, but do not clearly define their stage of differentiation. Introduction of visual transgenes into the cells of osteoblast lineage has revolutionized the field and resulted in a paradigm shift that allowed for specific identification and isolation of subpopulations within the osteoblast lineage. Knowledge acquired from the studies based on GFP transgenes has allowed for more precise interpretation of studies analyzing targeted overexpression or deletion of genes in the osteoblast lineage. Here, we provide a condensed overview of the currently available promoter-fluorescent reporter transgenic mice that have been generated and evaluated to varying extents. We cover different stages of the lineage as transgenes have been utilized to identify osteoprogenitors, pre-osteoblasts, osteoblasts, or osteocytes. We show that each of these promoters present with advantages and disadvantages. The studies based on the use of these reporter mice have improved our understanding of bone biology. They constitute attractive models to target osteoblasts and help to understand their cell biology.

7. Conclusion

Introduction of visual transgenes into the cells of the osteoblast lineage more than 15 years ago resulted in a major paradigm shift in how we look into different stages of osteogenic lineage maturation. Use of FP reporters allowed for identification and isolation of subpopulations of cells at different stages of lineage commitment. Currently, well characterized reporters are available for pre-osteoblasts (Col3.6), mature osteoblasts (Col2.3, BSP, Oc) and osteocytes (Dmp1). A number of reporters are also available for different osteoprogenitor populations, however there is still much to be learnt about the sources and identity of osteoprogenitors in vivo. Studies based on the use of these reporter mice have improved our understanding of bone biology. They are particularly useful for tracking cells into the osteoblast lineage, especially in an injury or transplantation setting where bone formation is often less organized than during normal growth. We anticipate that visual osteoblast lineage reporters will continue to contribute to our knowledge of basic bone biology, and well as to evaluate regenerative potential of different cell types.