Bone Formation.

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Technology Bone is a dynamic tissue, and is constantly remodeled via absorption by osteoblasts, and resorption by osteoclasts. This cyclical process goes awry in numerous bone-related disorders, for which, few remedies exist.     Transcription factors are important in bone remodeling. The inventors show that the absence of a zinc finger transcription factor called Shn3 in osteoblasts results in increased bone formation in vivo. Hence, inhibition of Shn3 provides a lucrative method of enhancing bone formation and mineralization (and vice-versa). Similarly, altering the expression or activity of another transcription factor called Shn2, would be useful for modulating trabecular bone formation and mineralization in the diaphysis of a bone, and growth plate maturation during endochondral ossification.     The inventors have further identified positive and negative regulators of osteoblastogenesis and osteoclastogenesis. A library of compounds can be tested to identify those that increase or decrease bone formation and mineralization based on their ability to modify the expression and/or activity of these regulators, or the differentiation of osteoblasts and osteoclasts from stem cells.    Further, the inventors have determined that the inhibition of ROBO signaling promotes osteoblast activity. High levels of protein expression were observed from 2 genes SLIT2 and SLIT3 in osteoblasts, and these ligands were shown to bind 2 receptors, ROBO1 and ROBO2. This set of ligands and receptors were shown to be involved in autocrine signaling. The inventors showed that the inhibition of this interaction would be an effective means of enhancing osteoblast differentiation resulting in enhanced bone formation and mineralization.