Osteomalacia and osteoporosis: evaluation of a diagnostic index.

Data from a retrospective study in 41 patients is used to suggest an index of bone disease. This is designed as a means of collating available results, clarifying the significance of each in diagnosing either osteomalacia or osteoporosis, and reducing the significance of a single abnormal finding--for example, a raised alkaline phosphatase activity or low serum 25 hydroxy vitamin D, when the overall index score is low. Index scores above 35% would be diagnostic of osteomalacia; scores below 15% if associated with collapsed vertebrae suggest osteoporosis. Scores between 15% and 35% would indicate the need for a bone biopsy to discriminate between osteoporosis and osteomalacia.

MiR-1 and miR-200 inhibit EMT via Slug-dependent and tumorigenesis via Slug-independent mechanisms.

Epithelial-mesenchymal transition (EMT) is a developmental program of signaling pathways that determine commitment to epithelial and mesenchymal phenotypes. In the prostate, EMT processes have been implicated in benign prostatic hyperplasia and prostate cancer progression. In a model of Pten- and TP53-null prostate adenocarcinoma that progresses via transforming growth factor ß-induced EMT, mesenchymal transformation is characterized by plasticity, leading to various mesenchymal lineages and the production of bone. Here we show that SLUG is a major regulator of mesenchymal differentiation. As microRNAs (miRs) are pleiotropic regulators of differentiation and tumorigenesis, we evaluated miR expression associated with tumorigenesis and EMT. Mir-1 and miR-200 were reduced with progression of prostate adenocarcinoma, and we identify Slug as one of the phylogenetically conserved targets of these miRs. We demonstrate that SLUG is a direct repressor of miR-1 and miR-200 transcription. Thus, SLUG and miR-1/miR-200 act in a self-reinforcing regulatory loop, leading to amplification of EMT. Depletion of Slug inhibited EMT during tumorigenesis, whereas forced expression of miR-1 or miR-200 inhibited both EMT and tumorigenesis in human and mouse model systems. Various miR targets were analyzed, and our findings suggest that miR-1 has roles in regulating EMT and mesenchymal differentiation through Slug and functions in tumor-suppressive programs by regulating additional targets.