We describe a novel role for CD271 in the differentiation of mesenchymal stem cells (MSCs), including deciduous dental pulp stem cells (DDPSCs) and murine multipotent MSCs (C3H10T1/2 cells). The CD271+ subpopulation of deciduous dental pulp cells (CD271+/DDPSCs) and the forced expression of CD271 in C3H10T1/2 (10T271) were analyzed by fluorescence-activated cell sorting. CD271 expression was detected in DDPSCs that expressed both CD44 and CD90, simultaneously, and the clonogenic capacity of the CD271+/DDPSCs was higher than that of the CD271−/DDPSCs that expressed both CD44 and CD90. Further, the differentiation of CD271+/DDPSCs into osteoblasts and adipocytes was inhibited although CD271−/DDPSCs were capable of differentiating into osteoblasts and adipocytes. CD271 was overexpressed in C3H10T1/2 cells, which have the potential to differentiate into osteoblasts, adipocytes, chondrocytes, and myocytes. CD271 inhibited the differentiation of C3H10T1/2 cells into any of these lineages. These results indicate a role for CD271 in inhibiting the differentiation of MSCs.
Get full access to this article
View all access options for this article.
References
1.
MischelPS, SmithSG, ViningER, VallettaJS, MobleyWC, ReichardtLF. 2001. The extracellular domain of p75NTR is necessary to inhibit neurotrophin-3 signaling through TrkA. J Biol Chem, 276:11294–11301.
2.
BothwellM. 1995. Functional interactions of neurotrophins and neurotrophin receptors. Annu Rev Neurosci, 18:223–253.
3.
Rodriguez-TebarA, DechantG, GotzR, BardeYA. 1992. Binding of neurotrophin-3 to its neuronal receptors and interactions with nerve growth factor and brain-derived neurotrophic factor. Embo J, 11:917–922.
4.
AntonES, WeskampG, ReichardtLF, MatthewWD. 1994. Nerve growth factor and its low-affinity receptor promote Schwann cell migration. Proc Natl Acad Sci USA, 91:2795–2799.
5.
HerrmannJL, MenterDG, HamadaJ, MarchettiD, NakajimaM, NicolsonGL. 1993. Mediation of NGF-stimulated extracellular matrix invasion by the human melanoma low-affinity p75 neurotrophin receptor: melanoma p75 functions independently of trkA. Mol Biol Cell, 4:1205–1216.
6.
RabizadehS, OhJ, ZhongLT, YangJ, BitlerCM, ButcherLL, BredesenDE. 1993. Induction of apoptosis by the low-affinity NGF receptor. Science, 261:345–348.
Casaccia-BonnefilP, CarterBD, DobrowskyRT, ChaoMV. 1996. Death of oligodendrocytes mediated by the interaction of nerve growth factor with its receptor p75. Nature, 383:716–719.
9.
CoulsonEJ, ReidK, BartlettPF. 1999. Signaling of neuronal cell death by the p75NTR neurotrophin receptor. Mol Neurobiol, 20:29–44.
10.
BarkerPA, ShooterEM. 1994. Disruption of NGF binding to the low affinity neurotrophin receptor p75LNTR reduces NGF binding to TrkA on PC12 cells. Neuron, 13:203–215.
11.
BamjiSX, MajdanM, PozniakCD, BelliveauDJ, AloyzR, KohnJ, CausingCG, MillerFD. 1998. The p75 neurotrophin receptor mediates neuronal apoptosis and is essential for naturally occurring sympathetic neuron death. J Cell Biol, 140:911–923.
12.
LeeKF, BachmanK, LandisS, JaenischR. 1994. Dependence on p75 for innervation of some sympathetic targets. Science, 263:1447–1449.
13.
Van der ZeeCE, RossGM, RiopelleRJ, HaggT. 1996. Survival of cholinergic forebrain neurons in developing p75NGFR-deficient mice. Science, 274:1729–1732.
14.
Levi-MontalciniR. 1987. The nerve growth factor 35 years later. Science, 237:1154–1162.
15.
BardeYA. 1989. Trophic factors and neuronal survival. Neuron, 2:1525–1534.
16.
ChaoMV. 1992. Neurotrophin receptors: a window into neuronal differentiation. Neuron, 9:583–593.
17.
BibelM, BardeYA. 2000. Neurotrophins: key regulators of cell fate and cell shape in the vertebrate nervous system. Genes Dev, 14:2919–2937.
18.
CampagnoloL, RussoMA, PuglianielloA, FavaleA, SiracusaG. 2001. Mesenchymal cell precursors of peritubular smooth muscle cells of the mouse testis can be identified by the presence of the p75 neurotrophin receptor. Biol Reprod, 64:464–472.
19.
SariolaH, SaarmaM, SainioK, ArumaeU, PalgiJ, VaahtokariA, ThesleffI, KaravanovA. 1991. Dependence of kidney morphogenesis on the expression of nerve growth factor receptor. Science, 254:571–573.
20.
HuberLJ, HempsteadB, DonovanMJ. 1996. Neurotrophin and neurotrophin receptors in human fetal kidney. Dev Biol, 179:369–381.
21.
LuukkoK, MoshnyakovM, SainioK, SaarmaM, SariolaH, ThesleffI. 1996. Expression of neurotrophin receptors during rat tooth development is developmentally regulated, independent of innervation, and suggests functions in the regulation of morphogenesis and innervation. Dev Dyn, 206:87–99.
22.
ByersMR, SchattemanGC, BothwellM. 1990. Multiple functions for NGF receptor in developing, aging and injured rat teeth are suggested by epithelial, mesenchymal and neural immunoreactivity. Development, 109:461–471.
23.
BoiretN, RapatelC, Veyrat-MassonR, GuillouardL, GuerinJJ, PigeonP, DescampsS, BoisgardS, BergerMG. 2005. Characterization of nonexpanded mesenchymal progenitor cells from normal adult human bone marrow. Exp Hematol, 33:219–225.
24.
AslanH, ZilbermanY, KandelL, LiebergallM, OskouianRJ, GazitD, GazitZ. 2006. Osteogenic differentiation of noncultured immunoisolated bone marrow-derived CD105+ cells. Stem Cells, 24:1728–1737.
25.
SimmonsPJ, Torok-StorbB. 1991. Identification of stromal cell precursors in human bone marrow by a novel monoclonal antibody, STRO-1. Blood, 78:55–62.
26.
QuiriciN, SoligoD, BossolascoP, ServidaF, LuminiC, DeliliersGL. 2002. Isolation of bone marrow mesenchymal stem cells by anti-nerve growth factor receptor antibodies. Exp Hematol, 30:783–791.
27.
BattulaVL, TremlS, BareissPM, GiesekeF, RoelofsH, de ZwartP, MullerI, ScheweB, SkutellaT, FibbeWE, KanzL, BuhringHJ. 2009. Isolation of functionally distinct mesenchymal stem cell subsets using antibodies against CD56, CD271, and mesenchymal stem cell antigen-1. Haematologica, 94:173–184.
28.
JarochaD, LukasiewiczE, MajkaM. 2008. Adventage of mesenchymal stem cells (MSC) expansion directly from purified bone marrow CD105+ and CD271+ cells. Folia Histochem Cytobiol, 46:307–314.
29.
BuhringHJ, BattulaVL, TremlS, ScheweB, KanzL, VogelW. 2007. Novel markers for the prospective isolation of human MSC. Ann NY Acad Sci, 1106:262–271.
MiuraM, GronthosS, ZhaoM, LuB, FisherLW, RobeyPG, ShiS. 2003. SHED: stem cells from human exfoliated deciduous teeth. Proc Natl Acad Sci USA, 100:5807–5812.
32.
GronthosS, MankaniM, BrahimJ, RobeyPG, ShiS. 2000. Postnatal human dental pulp stem cells (DPSCs) in vitro and in vivo. Proc Natl Acad Sci USA, 97:13625–13630.
33.
LainoG, GrazianoA, d'AquinoR, PirozziG, LanzaV, ValianteS, De RosaA, NaroF, VivarelliE, PapaccioG. 2006. An approachable human adult stem cell source for hard-tissue engineering. J Cell Physiol, 206:693–701.
TaylorSM, JonesPA. 1979. Multiple new phenotypes induced in 10T1/2 and 3T3 cells treated with 5-azacytidine. Cell, 17:771–779.
36.
KazamaT, FujieM, EndoT, KanoK. 2008. Mature adipocyte-derived dedifferentiated fat cells can transdifferentiate into skeletal myocytes in vitro. Biochem Biophys Res Commun, 377:780–785.
37.
MikamiY, SomeiM, TakagiM. 2009. A new synthetic compound, SST-VEDI-1, inhibits osteoblast differentiation with a down-regulation of the Osterix expression. J Biochem, 145:239–247.
38.
MikamiY, TakahashiT, KatoS, TakagiM. 2008. Dexamethasone promotes DMP1 mRNA expression by inhibiting negative regulation of Runx2 in multipotential mesenchymal progenitor, ROB-C26. Cell Biol Int, 32:239–246.
39.
LassarAB, PatersonBM, WeintraubH. 1986. Transfection of a DNA locus that mediates the conversion of 10T1/2 fibroblasts to myoblasts. Cell, 47:649–656.
40.
FischerL, BolandG, TuanRS. 2002. Wnt-3A enhances bone morphogenetic protein-2-mediated chondrogenesis of murine C3H10T1/2 mesenchymal cells. J Biol Chem, 277:30870–30878.
41.
PoloniA, MauriziG, RosiniV, MondiniE, ManciniS, DiscepoliG, BiasioS, BattagliniG, FelicettiS, BerardinelliE, SerraniF, LeoniP. 2009. Selection of CD271(+) cells and human AB serum allows a large expansion of mesenchymal stromal cells from human bone marrow. Cytotherapy, 11:153–162.
De BariC, Dell'AccioF, VanlauweJ, EyckmansJ, KhanIM, ArcherCW, JonesEA, McGonagleD, MitsiadisTA, PitzalisC, LuytenFP. 2006. Mesenchymal multipotency of adult human periosteal cells demonstrated by single-cell lineage analysis. Arthritis Rheum, 54:1209–1221.
44.
KhanWS, TewSR, AdesidaAB, HardinghamTE. 2008. Human infrapatellar fat pad-derived stem cells express the pericyte marker 3G5 and show enhanced chondrogenesis after expansion in fibroblast growth factor-2. Arthritis Res Ther, 10:R74.
45.
JonesEA, CrawfordA, EnglishA, HenshawK, MundyJ, CorscaddenD, ChapmanT, EmeryP, HattonP, McGonagleD. 2008. Synovial fluid mesenchymal stem cells in health and early osteoarthritis: detection and functional evaluation at the single-cell level. Arthritis Rheum, 58:1731–1740.
46.
KomoriT, YagiH, NomuraS, YamaguchiA, SasakiK, DeguchiK, ShimizuY, BronsonRT, GaoYH, InadaM, SatoM, OkamotoR, KitamuraY, YoshikiS, KishimotoT. 1997. Targeted disruption of Cbfa1 results in a complete lack of bone formation owing to maturational arrest of osteoblasts. Cell, 89:755–764.
47.
DucyP, ZhangR, GeoffroyV, RidallAL, KarsentyG. 1997. Osf2/Cbfa1: a transcriptional activator of osteoblast differentiation. Cell, 89:747–754.
48.
NakashimaK, ZhouX, KunkelG, ZhangZ, DengJM, BehringerRR, de CrombruggheB. 2002. The novel zinc finger-containing transcription factor osterix is required for osteoblast differentiation and bone formation. Cell, 108:17–29.
MoermanEJ, TengK, LipschitzDA, Lecka-CzernikB. 2004. Aging activates adipogenic and suppresses osteogenic programs in mesenchymal marrow stroma/stem cells: the role of PPAR-gamma2 transcription factor and TGF-beta/BMP signaling pathways. Aging Cell, 3:379–389.
51.
GoldringMB, TsuchimochiK, IjiriK. 2006. The control of chondrogenesis. J Cell Biochem, 97:33–44.
52.
LefebvreV, HuangW, HarleyVR, GoodfellowPN, de CrombruggheB. 1997. SOX9 is a potent activator of the chondrocyte-specific enhancer of the pro alpha1(II) collagen gene. Mol Cell Biol, 17:2336–2346.
53.
ZhangP, JimenezSA, StokesDG. 2003. Regulation of human COL9A1 gene expression. Activation of the proximal promoter region by SOX9. J Biol Chem, 278:117–123.
54.
BridgewaterLC, LefebvreV, de CrombruggheB. 1998. Chondrocyte-specific enhancer elements in the Col11a2 gene resemble the Col2a1 tissue-specific enhancer. J Biol Chem, 273:14998–15006.
55.
SekiyaI, TsujiK, KoopmanP, WatanabeH, YamadaY, ShinomiyaK, NifujiA, NodaM. 2000. SOX9 enhances aggrecan gene promoter/enhancer activity and is up-regulated by retinoic acid in a cartilage-derived cell line, TC6. J Biol Chem, 275:10738–10744.
56.
DedieuS, MazeresG, CottinP, BrustisJJ. 2002. Involvement of myogenic regulator factors during fusion in the cell line C2C12. Int J Dev Biol, 46:235–241.
57.
AndresV, WalshK. 1996. Myogenin expression, cell cycle withdrawal, and phenotypic differentiation are temporally separable events that precede cell fusion upon myogenesis. J Cell Biol, 132:657–666.
58.
LambiaseA, BoniniS, MiceraA, RamaP, AloeL. 1998. Expression of nerve growth factor receptors on the ocular surface in healthy subjects and during manifestation of inflammatory diseases. Invest Ophthalmol Vis Sci, 39:1272–1275.
TouhamiA, GrueterichM, TsengSC. 2002. The role of NGF signaling in human limbal epithelium expanded by amniotic membrane culture. Invest Ophthalmol Vis Sci, 43:987–994.
Al HalabiahH, DelezoideAL, CardonaA, MoalicJM, SimonneauM. 2005. Expression pattern of NOGO and NgR genes during human development. Gene Expr Patterns, 5:561–568.
66.
KomoriT. 2006. Regulation of osteoblast differentiation by transcription factors. J Cell Biochem, 99:1233–1239.
Supplementary Material
Please find the following supplemental material available below.
For Open Access articles published under a Creative Commons License, all supplemental material carries the same license as the article it is associated with.
For non-Open Access articles published, all supplemental material carries a non-exclusive license, and permission requests for re-use of supplemental material or any part of supplemental material shall be sent directly to the copyright owner as specified in the copyright notice associated with the article.
