title: Gene expression related to the differentiation of osteoblastic cells is altered by microgravity.
abstract: Bone loss is observed after exposure to weightlessness in both astronauts and inflight animals. Histological and biochemical studies on rats have shown a decrease in bone formation, probably as a result of altered osteoblast function. To investigate whether microgravity alters osteoblast differentiation in vitro, the human osteosarcoma cell line MG-63 was used as a model. MG-63 cells can be induced to differentiate by treating the cells with 1,25(OH)2D3 (10(-7) mol/L) and transforming growth factor-beta 2 (TGFbeta2) (10 ng/mL). The message level of differentiation-related genes was quantitated via competitive reverse transcription-polymerase chain reaction (RT-PCR), both in untreated and hormone-treated cells cultured under microgravity for 9 days aboard the unmanned Foton 10 spaceflight, and compared to ground and inflight unit-gravity cultures. At microgravity, gene expression for collagen Ialpha1 following treatment was reduced to 51% of unit-gravity levels (p < 0.05). The amount of alkaline phosphatase messenger ribonucleic acid (mRNA) following treatment at microgravity increased by only a factor of 5 compared to the tenfold increase at unit gravity (p < 0.02). The osteocalcin message level in treated cells cultured at microgravity was only 19% of the level found in cells grown at unit gravity (p < 0.02). In conclusion, microgravity reduces the differentiation of osteoblastic MG-63 cells in response to systemic hormones and growth factors.
authors.affiliation: Laboratorium voor Experimentele Geneeskunde en Endocrinologie, Katholieke Universiteit Leuven, Gasthuisberg, Belgium. geert.carmeliet@med.kuleuven.ac.be
authors.forename: G
authors.initials: G
authors.lastname: Carmeliet
authors.forename: G
authors.initials: G
authors.lastname: Nys
authors.forename: I
authors.initials: I
authors.lastname: Stockmans
authors.forename: R
authors.initials: R
authors.lastname: Bouillon
mesh_terms: D000469:Alkaline Phosphatase / Q000235:genetics / Q000378:metabolism*; D002117:Calcitriol / Q000494:pharmacology; D002454:Cell Differentiation; D002478:Cells, Cultured; D003094:Collagen / Q000235:genetics / Q000378:metabolism*; D004338:Drug Combinations; D015870:Gene Expression; D006801:Humans; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D015675:Osteocalcin / Q000235:genetics / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000494:pharmacology; D014893:Weightlessness
chemical_list: D004338:Drug Combinations; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D015675:Osteocalcin; D003094:Collagen; D000469:Alkaline Phosphatase; D002117:Calcitriol