Metallofullerene nanoparticles promote osteogenic differentiation of bone marrow stromal cells through BMP signaling pathway.

Although endohedral metallofullerenol [Gd@C(82)(OH)(22)](n) nanoparticles have anti-tumor efficiency and mostly deposit in the bones of mice, how these nanoparticles act in bone marrow stromal cells (MSCs) remains largely unknown. Herein, we observed that [Gd@C(82)(OH)(22)](n) nanoparticles facilitated the differentiation of MSCs toward osteoblasts, as evidenced by the enhancement of alkaline phosphatase (ALP) activity and mineralized nodule formation upon [Gd@C(82)(OH)(22)](n) nanoparticle treatment. Mechanistically, the effect of [Gd@C(82)(OH)(22)](n) nanoparticles on ALP activity was inhibited by the addition of noggin as an inhibitor of the BMP signaling pathway. Moreover, the in vivo results of the ovariectomized rats further indicated that [Gd@C(82)(OH)(22)](n) nanoparticles effectively improved bone density and prevented osteoporosis.

[1]  Thanh Yen Nguyen,et al.  Nanophase hydroxyapatite and poly(lactide-co-glycolide) composites promote human mesenchymal stem cell adhesion and osteogenic differentiation in vitro , 2012, Journal of Materials Science: Materials in Medicine.

[2]  Michael Goodman,et al.  Distribution, elimination, and biopersistence to 90 days of a systemically introduced 30 nm ceria-engineered nanomaterial in rats. , 2012, Toxicological sciences : an official journal of the Society of Toxicology.

[3]  L. Qin,et al.  Impaired bone healing pattern in mice with ovariectomy-induced osteoporosis: A drill-hole defect model. , 2011, Bone.

[4]  F. Peyrin,et al.  Evaluation of bone scaffolds by micro-CT , 2011, Osteoporosis International.

[5]  Yun Sun,et al.  Fluorine-18 labeled rare-earth nanoparticles for positron emission tomography (PET) imaging of sentinel lymph node. , 2011, Biomaterials.

[6]  C. Yi,et al.  Gold nanoparticles promote osteogenic differentiation of mesenchymal stem cells through p38 MAPK pathway. , 2010, ACS nano.

[7]  F. Guillemot,et al.  Retinoic acid regulates bone morphogenic protein signal duration by promoting the degradation of phosphorylated Smad1 , 2010, Proceedings of the National Academy of Sciences.

[8]  Wei Bai,et al.  Lung deposition and extrapulmonary translocation of nano-ceria after intratracheal instillation , 2010, Nanotechnology.

[9]  Y. Cho,et al.  Rapamycin promotes the osteoblastic differentiation of human embryonic stem cells by blocking the mTOR pathway and stimulating the BMP/Smad pathway. , 2010, Stem cells and development.

[10]  C. Yi,et al.  Inhibition of proliferation and differentiation of mesenchymal stem cells by carboxylated carbon nanotubes. , 2010, ACS nano.

[11]  Q. Wang,et al.  Regulation of osteogenic differentiation of rat bone marrow stromal cells on 2D nanorod substrates. , 2010, Biomaterials.

[12]  C. Yi,et al.  Effects of carbon nanotubes on the proliferation and differentiation of primary osteoblasts. , 2010, Methods in molecular biology.

[13]  Xia Li,et al.  BMP signaling pathway is required for commitment of C3H10T1/2 pluripotent stem cells to the adipocyte lineage , 2009, Proceedings of the National Academy of Sciences.

[14]  Y. Liu,et al.  The effect of Gd@C82(OH)22 nanoparticles on the release of Th1/Th2 cytokines and induction of TNF-alpha mediated cellular immunity. , 2009, Biomaterials.

[15]  R. Reis,et al.  The osteogenic differentiation of rat bone marrow stromal cells cultured with dexamethasone-loaded carboxymethylchitosan/poly(amidoamine) dendrimer nanoparticles. , 2009, Biomaterials.

[16]  S. Shen,et al.  Effect of Dy3+on osteogenic and adipogenic differentiation of mouse primary bone marrow stromal cells and adipocytic trans-differentiation of mouse primary osteoblasts , 2009 .

[17]  Warren C W Chan,et al.  Nanoparticle-mediated cellular response is size-dependent. , 2008, Nature nanotechnology.

[18]  K. Beggs,et al.  Osteogenic Gene Expression by Human Periodontal Ligament Cells under Cyclic Tension , 2007, Journal of dental research.

[19]  J. Park,et al.  Wound healing effect of adipose-derived stem cells: a critical role of secretory factors on human dermal fibroblasts. , 2007, Journal of dermatological science.

[20]  P. Xiao,et al.  Effect of zinc ion on the osteogenic and adipogenic differentiation of mouse primary bone marrow stromal cells and the adipocytic trans-differentiation of mouse primary osteoblasts. , 2007, Journal of trace elements in medicine and biology : organ of the Society for Minerals and Trace Elements.

[21]  P. de Vos,et al.  Zeta-potentials of alginate-PLL capsules: a predictive measure for biocompatibility? , 2007, Journal of biomedical materials research. Part A.

[22]  S. Fricker The therapeutic application of lanthanides. , 2006, Chemical Society reviews.

[23]  Z. Chai,et al.  Antioxidative function and biodistribution of [Gd@C82(OH)22]n nanoparticles in tumor-bearing mice. , 2006, Biochemical pharmacology.

[24]  M. Mann,et al.  Differential Expression Profiling of Membrane Proteins by Quantitative Proteomics in a Human Mesenchymal Stem Cell Line Undergoing Osteoblast Differentiation , 2005, Stem cells.

[25]  Feng Zhao,et al.  Multihydroxylated [Gd@C82(OH)22]n nanoparticles: antineoplastic activity of high efficiency and low toxicity. , 2005, Nano letters.

[26]  J. Wands,et al.  Hepatitis C virus core protein stimulates hepatocyte growth: Correlation with upregulation of wnt‐1 expression , 2005, Hepatology.

[27]  Z. Chai,et al.  Tuning electronic properties of metallic atom in bondage to a nanospace. , 2005, The journal of physical chemistry. B.

[28]  Xu Cao,et al.  BMP signaling in skeletal development. , 2005, Biochemical and biophysical research communications.

[29]  Z. Chai,et al.  Influences of Structural Properties on Stability of Fullerenols. , 2004, The journal of physical chemistry. B.

[30]  M. Goumans,et al.  Controlling cell fate by bone morphogenetic protein receptors , 2003, Molecular and Cellular Endocrinology.

[31]  Chunli Song,et al.  Simvastatin induces osteoblastic differentiation and inhibits adipocytic differentiation in mouse bone marrow stromal cells. , 2003, Biochemical and biophysical research communications.

[32]  T. Komori Requisite roles of Runx2 and Cbfb in skeletal development , 2003, Journal of Bone and Mineral Metabolism.

[33]  B. Spiegelman,et al.  Genetic Analysis of Adipogenesis through Peroxisome Proliferator-activated Receptor γ Isoforms* , 2002, The Journal of Biological Chemistry.

[34]  M. Demay,et al.  Cloning and Characterization of a Novel WD-40 Repeat Protein That Dramatically Accelerates Osteoblastic Differentiation* , 2001, The Journal of Biological Chemistry.

[35]  J. Gimble,et al.  Is there a therapeutic opportunity to either prevent or treat osteopenic disorders by inhibiting marrow adipogenesis? , 2000, Bone.

[36]  P. Delmas,et al.  Influence of mature adipocytes on osteoblast proliferation in human primary cocultures. , 2000, Bone.

[37]  K. Miyazono,et al.  Roles of bone morphogenetic protein type I receptors and Smad proteins in osteoblast and chondroblast differentiation. , 1999, Molecular biology of the cell.

[38]  S. Kennel,et al.  In vivo studies of fullerene-based materials using endohedral metallofullerene radiotracers. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[39]  B. Spiegelman,et al.  Cross-Regulation of C/EBPα and PPARγ Controls the Transcriptional Pathway of Adipogenesis and Insulin Sensitivity , 1999 .

[40]  V. Rosen,et al.  Differential Roles for Bone Morphogenetic Protein (BMP) Receptor Type IB and IA in Differentiation and Specification of Mesenchymal Precursor Cells to Osteoblast and Adipocyte Lineages , 1998, The Journal of cell biology.

[41]  J. Gimble,et al.  1,25-Dihydroxy vitamin D3 inhibits adipocyte differentiation and gene expression in murine bone marrow stromal cell clones and primary cultures. , 1998, Endocrinology.

[42]  B. Spiegelman,et al.  15-Deoxy-Δ 12,14-Prostaglandin J 2 is a ligand for the adipocyte determination factor PPARγ , 1995, Cell.

[43]  G S Stein,et al.  Molecular mechanisms mediating proliferation/differentiation interrelationships during progressive development of the osteoblast phenotype. , 1993, Endocrine reviews.

[44]  A. G. Taylor,et al.  The role of alkaline phosphatase in cartilage mineralization. , 1992, Bone and mineral.

[45]  C. Devlin,et al.  Evidence for an inverse relationship between the differentiation of adipocytic and osteogenic cells in rat marrow stromal cell cultures. , 1992, Journal of cell science.

[46]  J. Gordon,et al.  Tissue-specific expression, developmental regulation, and genetic mapping of the gene encoding CCAAT/enhancer binding protein. , 1989, Genes & development.

[47]  B. Beutler,et al.  Purification of cachectin, a lipoprotein lipase-suppressing hormone secreted by endotoxin-induced RAW 264.7 cells , 1985, The Journal of experimental medicine.