PMID- 9275074 OWN - NLM STAT- MEDLINE DCOM- 19970918 LR - 20131121 IS - 0013-7227 (Print) IS - 0013-7227 (Linking) VI - 138 IP - 9 DP - 1997 Sep TI - Multiple extracellular signals promote osteoblast survival and apoptosis. PG - 3849-58 AB - Programed cell death (PCD) or apoptosis is a naturally occurring cell suicide pathway induced in a variety of cell types. In many cases, PCD apparently arises as a result of competition for limiting amounts of survival signals. In this study, we have investigated the potential role of growth factors (GF), cytokines, and osteotropic hormones on osteoblast survival in vitro. Our results indicate that in the absence of any of these factors, osteoblasts rapidly undergo PCD, as determined by cell morphology, mitochondrial function, and nuclei fragmentation. Osteoblast survival was promoted by insulin-like growth factor I (IGF-I), IGF-II, insulin, and basic fibroblast growth factor (bFGF). Platelet-derived growth factor had no effect on osteoblast survival, but this GF potentiated the survival-promoting effects of IGF-I, IGF-II, and insulin. A similar effect occurred when bFGF was added in combination with either of the IGFs or insulin. The effects of the IGFs were blocked by alphaIR-3, an antibody to the type I IGF receptor, whereas the effects of insulin were only partially blocked. This antibody blocked the potentiating effects of platelet-derived growth factor on IGF-I-mediated osteoblast survival, but only partially blocked those of bFGF. Although a 100% survival of osteoblasts was seen in the presence of 2% FCS, the highest level attained by any of the above GF combinations was approximately 75%. The monocyte-derived factor, tumor necrosis factor-alpha (TNF alpha) was the only agent that enhanced PCD in this study. These results suggest that osteoblast survival is promoted by those GFs sequestrated in bone matrix and that the type I, but not the type II, IGF receptor is involved in the response. Our data also indicate that other unidentified GFs or components of the extracellular matrix may be involved in promoting osteoblast survival and that TNF alpha may abrogate their effects in vivo. We propose that these GFs may be released from bone matrix during phases of bone resorption and promote osteoblast survival, thereby playing an important role in bone remodeling, and that PCD induced by TNF alpha may contribute to the bone loss in inflammatory bone disease. FAU - Hill, P A AU - Hill PA AD - Department of Orthodontics and Pediatric Dentistry, United Medical and Dental Schools of Guy's and St. Thomas' Hospitals, University of London, United Kingdom. FAU - Tumber, A AU - Tumber A FAU - Meikle, M C AU - Meikle MC LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Endocrinology JT - Endocrinology JID - 0375040 RN - 0 (Antibodies) RN - 0 (Growth Substances) RN - 0 (Insulin) RN - 0 (Parathyroid Hormone) RN - 103107-01-3 (Fibroblast Growth Factor 2) RN - 67763-96-6 (Insulin-Like Growth Factor I) RN - 67763-97-7 (Insulin-Like Growth Factor II) RN - EC 2.7.10.1 (Receptor, IGF Type 1) RN - FXC9231JVH (Calcitriol) SB - IM MH - Animals MH - Antibodies/pharmacology MH - *Apoptosis MH - Calcitriol/pharmacology MH - *Cell Survival MH - Cells, Cultured MH - DNA Fragmentation MH - Fibroblast Growth Factor 2/pharmacology MH - Growth Substances/*pharmacology MH - Humans MH - Insulin/pharmacology MH - Insulin-Like Growth Factor I/pharmacology MH - Insulin-Like Growth Factor II/pharmacology MH - Mice MH - Mitochondria/physiology MH - Osteoblasts/*physiology/ultrastructure MH - Parathyroid Hormone MH - Receptor, IGF Type 1/antagonists & inhibitors/physiology MH - *Signal Transduction EDAT- 1997/09/01 00:00 MHDA- 1997/09/01 00:01 CRDT- 1997/09/01 00:00 PHST- 1997/09/01 00:00 [pubmed] PHST- 1997/09/01 00:01 [medline] PHST- 1997/09/01 00:00 [entrez] AID - 10.1210/endo.138.9.5370 [doi] PST - ppublish SO - Endocrinology. 1997 Sep;138(9):3849-58. doi: 10.1210/endo.138.9.5370.