Rapid differentiation of MSC into adipocytes and osteocytes is facilitated by Toll-Like receptor engagement

Date

2010-04-01

Author

Tas, Ibrahim
Tokcaer-Keskin, Zeynep
Ayhan, Fatma
Gürsel, Mayda
Akcali, Kamil

Metadata

Show full item record

This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

Item Usage Stats

233
views

0
downloads

Mesenchymal stem cells are multipotent progenitor cells capable of differentiating into several lineages including adipocytes, and osteocytes. While they are regarded as non-immunogenic, accumulating evidence suggests that MSC expresses several TLRs. We checked the contribution of TLR ligands to MSC differentiation. Rat bone marrow derived MSC surface marker and TLR transcript levels were checked by FACS and RT-PCR respectively. MSCs were CD29hi, CD71dim, CD90hi, and negative for CD45 & CD34. They expressed TLR1,2,3,4,6, and low levels of 7 and 9 (no TLR5 was detected) at passage zero. Cells were incubated in adipogenic and osteogenic differentiation media either alone or supplemented with, TLR2L:PGN, TLR3L:pI:C, TLR7L:R848, and TLR9L:CpGODN as well as control ODN and followed for three weeks. Oil Red O staining (to assess adipogenesis) suggested that, induction in adipogenic media (by one week) gave no adipose positive cells whereas treatment with R848 or PGN induced significantly high adipose positive cells (1-2% vs 30-35%, respectively). The degree of adipogenic differentiation at wk1, was; TLR7≥TLR2>TLR3>TLR9>Control group≥medium. During osteogenesis (checked by alizarin red staining) by one week the highest differentiation was seen with CpG ODN treatment (TLR9≥TLR7>TLR2>TLR3>Control≥medium). These results strongly support the view that TLR ligands differentially contribute to transition of MSCs into either adipogenic or osteogenic differentiation.

Subject Keywords

Immunology

URI

https://hdl.handle.net/11511/52720

Journal

JOURNAL OF IMMUNOLOGY

Collections

Department of Biology, Article

Suggestions

OpenMETU
Core

Cutting edge: Role of toll-like receptor 9 in CpG DNA-induced activation of human cells Takeshita, F; Leifer, CA; Gursel, I; Ishii, KJ; Takeshita, S; Gürsel, Mayda; Klinman, DM (The American Association of Immunologists, 2001-10-01) Unmethylated CpG motifs present in bacterial DNA stimulate a rapid and robust innate immune response. Human cell lines and PBMC that recognize CpG DNA express membrane-bound human Toll-like receptor 9 (hTLR9). Cells that are not responsive to CpG DNA become responsive when transfected with hTLR9. Expression of hTLR9 dramatically increases uptake of CpG (but not control) DNA into endocytic vesicles. Upon cell stimulation, hTLR9 and CpG DNA are found in the same endocytic vesicles. Cells expressing hTLR9 are ...
CpG RNA: identification of novel single-stranded RNA that stimulates human CD14+CD11c+ monocytes. Sugiyama, T; Gürsel, Mayda; Takeshita, F; Coban, C; Conover, J; Kaisho, T; Akira, S; Klinman, DM; Ishii, KJ (The American Association of Immunologists, 2005-02-15) Synthetic immunostimulatory nucleic acids such as CpG DNA are being harnessed therapeutically as vaccine adjuvants, anticancer or antiallergic agents. Efforts to identify nucleic acid-based agents capable of more specifically modulating the immune system are being developed. The current study identifies a novel class of single-stranded oligoribonucleotides (ORN) containing unmethylated CpG motifs and a poly(G) run at the 3 end (CpG ORN) that directly stimulate human CD14 CD11c monocytes but not dendritic ...
Suppressive oligodeoxynucleotides inhibit Th1 differentiation by blocking IFN-gamma- and IL-12-mediated signaling. Shirota, H; Gürsel, Mayda; Klinman, DM (The American Association of Immunologists, 2004-10-15) Repetitive TTAGGG motifs present at high frequency in mammalian telomeres can suppress Th1-mediated immune responses. Synthetic oligonucleotides (ODN) containing TTAGGG motifs mimic this activity and have proven effective in the prevention/ treatment of certain Th1-dependent autoimmune diseases. This work explores the mechanism by which suppressive ODN block the induction of Th1 immunity. Findings indicate that these ODN inhibit IFN- -induced STAT1 phosphorylation and IL-12- induced STAT3 and STAT4 phosphor...
CpG oligodeoxynucleotides protect normal and SIV-infected macaques from Leishmania infection. Verthelyi, D; Gürsel, Mayda; Kenney, RT; Lifson, JD; Liu, S; Mican, J; Klinman, DM (The American Association of Immunologists, 2003-05-01) Oligodeoxynucleotides containing CpG motifs (CpG ODNs) mimic microbial DNA and activate effectors of the innate immune response, which limits the spread of pathogens and promotes an adaptive immune response. CpG ODNs have been shown to protect mice from infection with intracellular pathogens. Unfortunately, CpG motifs that optimally stimulate humans are only weakly active in mice, mandating the use of nonhuman primates to monitor the activity and safety of "human" CpG ODNs in vivo. This study demonstrates t...
Repetitive elements in mammalian telomeres suppress bacterial DNA-induced immune activation. Gursel, I; Gürsel, Mayda; Yamada, H; Ishii, KJ; Takeshita, F; Klinman, DM (The American Association of Immunologists, 2003-08-01) Bacterial DNA contains immunostimulatory CpG motifs that trigger an innate immune response capable of promoting host survival following infectious challenge. Yet CpG-driven immune activation may also have deleterious consequences, ranging from autoimmune disease to death. We find that repetitive elements present at high frequency in mammalian telomeres, but rare in bacteria, down-regulate CpG-induced immune activation. Suppressive activity correlates with the ability of telomeric TTAGGG repeats to form G-te...

Citation Formats

I. Tas, Z. Tokcaer-Keskin, F. Ayhan, M. Gürsel, and K. Akcali, “Rapid differentiation of MSC into adipocytes and osteocytes is facilitated by Toll-Like receptor engagement,” JOURNAL OF IMMUNOLOGY, pp. 0–0, 2010, Accessed: 00, 2020. [Online]. Available: https://hdl.handle.net/11511/52720.