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In this pilot study, we investigated the dose\u2010response to 1\u03b1,25\u2010dihdroxyvitamin D<jats:sub>3<\/jats:sub> (1,\u03b1 25(OH)<jats:sub>2<\/jats:sub>D<jats:sub>3<\/jats:sub>) and 25\u2010hydroxyvitamin D<jats:sub>3<\/jats:sub> (25(OH)D<jats:sub>3<\/jats:sub>) by human OS cell lines, SaOS\u20102, and 143B. We hypothesized that 1,\u03b1 25(OH)<jats:sub>2<\/jats:sub>D<jats:sub>3<\/jats:sub> and 25(OH)D<jats:sub>3<\/jats:sub> would stimulate differentiation and induce apoptosis in OS cells in a dose\u2010dependent manner. Human OS cell lines, SaOS\u20102, and 143B, were treated with 1,\u03b1 25(OH)<jats:sub>2<\/jats:sub>D<jats:sub>3<\/jats:sub> or 25(OH)D<jats:sub>3<\/jats:sub> or an ethanol control, respectively, at concentrations ranging from 1 to 1,000\u2009nM. Ki67 (a marker of cellular proliferation) immunocytochemistry revealed no significant changes in the expression of Ki\u201067 or MIB\u20101 in 1\u03b1,25(OH)<jats:sub>2<\/jats:sub>D<jats:sub>3<\/jats:sub> or 25(OH)D<jats:sub>3<\/jats:sub> treated SaOS\u20102 or 143B cells. Both control and 1\u03b1,25(OH)<jats:sub>2<\/jats:sub>D<jats:sub>3<\/jats:sub> treated SaOS\u20102 and 143B cells expressed vitamin D receptor (VDR). Markers of osteoblastic differentiation in 143B cells and SaOS\u20102 cells were induced by both 25(OH)D<jats:sub>3<\/jats:sub> and 1\u03b1,25(OH)<jats:sub>2<\/jats:sub>D, and evident by increases in alkaline phosphatase (ALP) activity, osteocalcin (OCN) mRNA expression, and mineralization of extra\u2010cellular matrix (ECM) by alizarin red staining. An increasing trend in apoptosis in response to 25(OH)D<jats:sub>3<\/jats:sub>, in both SaOS\u20102 and 143B cells was detected by terminal deoxynucleotidyl transferase (TdT)\u2010mediated dUTP nick end labeling (TUNEL) staining. With 1\u03b1,25(OH)<jats:sub>2<\/jats:sub>D<jats:sub>3<\/jats:sub> treatment, apoptosis was evident at higher concentrations only. These preliminary findings suggest that OS cells express VDR and respond to 25(OH)D<jats:sub>3<\/jats:sub> and 1\u03b1,25(OH)<jats:sub>2<\/jats:sub>D<jats:sub>3<\/jats:sub> by undergoing differentiation and apoptosis. \u00a9 2011 Orthopaedic Research Society Published by Wiley Periodicals, Inc. 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