p73 is essential for vitamin D-mediated osteoblastic differentiation.
The secosteroid hormone vitamin D3 (VD3) exerts its biological actions through its cognate receptor, the vitamin D receptor (VDR). Vitamin D3 and VDR have a key function in bone formation and keratinocyte differentiation, exert antiproliferative actions in human cancer, and is widely used as a chemotherapeutic agent for cancer. In addition, VD3 promotes differentiation of human osteosarcoma cells by up-regulating genes involved in cell cycle arrest and osteoblastic differentiation. Although considerable work has been carried out in understanding the molecular mechanisms underlying the VD3-mediated differentiation of human osteosarcoma cells, the upstream regulation of VD3 signaling pathway is still unclear. In this study, we show that p73 acts as an upstream regulator of VD3-mediated osteoblastic differentiation. Transcription factor p73, a p53 homolog, has been shown to have a function in development and recently been termed as a tumor suppressor. Silencing p73 results in a significant reduction of VD3-mediated osteoblastic differentiation; although DNA damage induced p73 leads to an increase in VD3-mediated differentiation of osteosarcoma cells. Together, our data implicate a novel function for p73 in vitamin D-mediated differentiation of human osteosarcoma cells.
Department of Biochemistry and Molecular Biology, Boonshoft School of Medicine, Wright State University, 3640 Colonel Glenn Highway, Dayton, OH 45435, USA.
R
R
Kommagani
A
A
Whitlatch
M K
MK
Leonard
M P
MP
Kadakia
D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D045744:Cell Line, Tumor; D004249:DNA Damage; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects* / Q000502:physiology*; D015675:Osteocalcin / Q000235:genetics / Q000378:metabolism; D053495:Osteopontin / Q000235:genetics / Q000378:metabolism; D012516:Osteosarcoma / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D018167:Receptors, Calcitriol / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D000072160:Tumor Protein p73; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*; D014807:Vitamin D / Q000494:pharmacology*
D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D034741:RNA, Small Interfering; D018167:Receptors, Calcitriol; C000606460:TP73 protein, human; D000072160:Tumor Protein p73; D025521:Tumor Suppressor Proteins; D015675:Osteocalcin; D053495:Osteopontin; D014807:Vitamin D