Bone morphogenetic protein signaling is involved in human mesenchymal stem cell survival in serum-free medium.
Bone marrow human mesenchymal stem cells (hMSCs) are known to survive in serum-free media, when most normal somatic cells do not survive. We found that the endogenously-activated bone morphogenetic protein (BMP) pathway is involved in this cellular behavior. Under this culture condition, phosphorylated Smad1 (PSmad1), the transducer of this signal, is localized in the hMSC nuclei. In addition, inhibition of this pathway with noggin, a BMP antagonist, elicits a caspase-dependent hMSC's death in a concentration-dependent manner. Furthermore, exogenously added BMP4 alleviates the noggin effect, restoring cell survival, and suggesting that BMP signal is essential for hMSC survival under serum deprivation conditions. Altogether these findings demonstrate for the first time an endogenous survival pathway of hMSCs driven by a BMP signal. Such a survival mechanism might be involved in the maintenance of the hMSC population within their bone marrow niche.
Solmesky
Leonardo J
LJ
Department of Cell Research and Immunology, Faculty of Life Sciences, Tel Aviv University, Tel Aviv 69978, Israel.
Abekasis
Michal
M
Bulvik
Shlomo
S
Weil
Miguel
M
D000293:Adolescent; D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000032:analysis; D055396:Bone Morphogenetic Protein 2 / Q000235:genetics* / Q000378:metabolism / Q000494:pharmacology; D055415:Bone Morphogenetic Protein 4 / Q000235:genetics* / Q000378:metabolism / Q000494:pharmacology; D002453:Cell Cycle / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D016895:Culture Media, Serum-Free / Q000494:pharmacology; D005434:Flow Cytometry; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D007150:Immunohistochemistry; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D008875:Middle Aged; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics* / Q000502:physiology; D051898:Smad1 Protein / Q000235:genetics / Q000378:metabolism; D055815:Young Adult
D015703:Antigens, CD; D055396:Bone Morphogenetic Protein 2; D055415:Bone Morphogenetic Protein 4; D016895:Culture Media, Serum-Free; C497399:SMAD1 protein, human; D051898:Smad1 Protein