Two of four alternatively spliced isoforms of RUNX2 control osteocalcin gene expression in human osteoblast cells.

Runx2 is a Runt domain transcription factor that transcriptionally regulates osteoblast differentiation and bone formation. In this study, we show that human chondro- and osteosarcoma cell lines, human mesenchymal stem cells (hMSC) and a human primary chondrocytes (HC), osteoblst cells (HOb) express an intact isoform (RUNX2wt) and 3 alternatively spliced isoforms (RUNX2Delta5, Delta7, and Delta5Delta7) that are generated by skipping exon 5 and/or exon 7. Two of the truncated forms of RUNX2 (RUNX2Delta5 and RUNX2Delta5Delta7) did not localize in the nucleus and had lost their DNA binding activity.

Synthesis and structure-activity relationships of 16-ene-22-thia-1alpha,25-dihydroxy-26,27-dimethyl-19-norvitamin D3 analogs having side chains of different sizes.

We have synthesized eight novel 16-ene-22-thia-26,27-dimethyl-19-norvitamin D3 analogs 1-5 bearing side chains of different sizes, in combination with 20S- and 20R-isomers. The target compounds were prepared by Wittig-Horner reaction of A-ring phosphine oxide with 16-ene-22-thia-25-hydroxy Grundmann's ketones having different sized side chains, which were derived from the S-phenyloxycarbonyl derivative 13 as key intermediates. The binding affinity to the vitamin D receptor (VDR), VDR-mediated transcriptional activity, and osteoclast-inducing activity of synthetic 22-thia-19-norvitamin D analogs 1-5 were investigated.