Gene expression related to the differentiation of osteoblastic cells is altered by microgravity.
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.
Carmeliet
G
G
Laboratorium voor Experimentele Geneeskunde en Endocrinologie, Katholieke Universiteit Leuven, Gasthuisberg, Belgium. geert.carmeliet@med.kuleuven.ac.be
Nys
G
G
Stockmans
I
I
Bouillon
R
R
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
D004338:Drug Combinations; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D015675:Osteocalcin; D003094:Collagen; D000469:Alkaline Phosphatase; D002117:Calcitriol