title: The oncofetal gene survivin promotes cell proliferation and survival in primary human osteoblastic cells.
abstract: Survivin, the smallest member of the inhibitor of apoptosis gene family, is critical for the regulation of mitosis and maintenance of cell viability during embryonic development and cancer, while not being detectable in most adult differentiated tissues. We know little about whether survivin plays any physiological or pathophysiological role in the adult musculoskeletal system. We studied the expression of survivin in primary human osteoblastic cells and its biological functions in vitro. Survivin was detected by immunoblotting and real-time PCR. Subcellular localization was analyzed by immunofluorescence. Transfection of siRNA and plasmids coding for wild-type survivin was performed to study survivin function, i.e., proliferation and apoptosis assays. Survivin mRNA and protein are expressed in primary human osteoblastic cells. During interphase survivin localizes predominantly to the cytoplasmic compartment, which is relevant for the organization of the spindle apparatus during mitosis. Survivin knockdown resulted in an arrest of the cell cycle at the G(2)/M phase and increased rates of apoptosis. Elevated levels of survivin in primary human osteoblasts enhanced proliferation and cell viability. Taken together, we demonstrate for the first time that survivin is expressed in primary human osteoblastic cells on the mRNA and protein levels. Our results indicate that survivin is a critical factor for cell division and cell viability in primary human osteoblastic cells. Learning more about survivin's role in human osteoblasts could be an important step toward understanding the complex processes involved in bone homeostasis and remodeling.
authors.affiliation: Department of Orthopedic Surgery, University of Regensburg, Asklepios Klinikum Bad Abbach, Germany. p.lechler@asklepios.com
authors.forename: Philipp
authors.initials: P
authors.lastname: Lechler
authors.forename: Jens
authors.initials: J
authors.lastname: Schaumburger
authors.forename: Franz X
authors.initials: FX
authors.lastname: Köck
authors.forename: Sanjeevi
authors.initials: S
authors.lastname: Balakrishnan
authors.forename: Stavros
authors.initials: S
authors.lastname: Doukas
authors.forename: Lukas
authors.initials: L
authors.lastname: Prantl
authors.forename: Joachim
authors.initials: J
authors.lastname: Grifka
mesh_terms: D000951:Antigens, Neoplasm / Q000235:genetics / Q000494:pharmacology / Q000502:physiology; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects / Q000235:genetics; D002478:Cells, Cultured; D005786:Gene Expression Regulation / Q000187:drug effects; D055785:Gene Knockdown Techniques; D006367:HeLa Cells; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000494:pharmacology / Q000502:physiology*; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D061251:Primary Cell Culture; D034741:RNA, Small Interfering / Q000494:pharmacology; D000077022:Survivin; D014162:Transfection; D015854:Up-Regulation / Q000187:drug effects / Q000235:genetics
chemical_list: D000951:Antigens, Neoplasm; C107489:BIRC5 protein, human; D051034:Inhibitor of Apoptosis Proteins; D034741:RNA, Small Interfering; D000077022:Survivin; C031192:oncofetal antigens