GONUTS has been updated to MW1.31 Most things seem to be working but be sure to report problems.

Have any questions? Please email us at ecoliwiki@gmail.com

PMID:20032469

From GONUTS
Jump to: navigation, search
Citation

Bilkovski, R, Schulte, DM, Oberhauser, F, Gomolka, M, Udelhoven, M, Hettich, MM, Roth, B, Heidenreich, A, Gutschow, C, Krone, W and Laudes, M (2010) Role of WNT-5a in the determination of human mesenchymal stem cells into preadipocytes. J. Biol. Chem. 285:6170-8

Abstract

Increasing adipocyte size as well as numbers is important in the development of obesity and type 2 diabetes, with adipocytes being generated from mesenchymal precursor cells. This process includes the determination of mesenchymal stem cells (MSC) into preadipocytes (PA) and the differentiation of PA into mature fat cells. Although the process of differentiation has been highly investigated, the determination in humans is poorly understood. In this study, we compared human MSC and human committed PA on a cellular and molecular level to gain further insights into the regulatory mechanisms in the determination process. Both cell types showed similar morphology and expression patterns of common mesenchymal and hematopoietic surface markers. However, although MSC were able to differentiate into adipocytes and osteocytes, PA were only able to undergo adipogenesis, indicating that PA lost their multipotency during determination. WNT-5a expression showed significantly higher levels in MSC compared with PA suggesting that WNT-5a down-regulation might be important in the determination process. Indeed, incubation of human MSC in medium containing neutralizing WNT-5a antibodies abolished their ability to undergo osteogenesis, although adipogenesis was still possible. An opposite effect was achieved using recombinant WNT-5a protein. On a molecular level, WNT-5a was found to promote c-Jun N-terminal kinase-dependent intracellular signaling in MSC. Activation of this noncanonical pathway resulted in the induction of osteopontin expression further indicating pro-osteogenic effects of WNT-5a. Our data suggest that WNT-5a is necessary to maintain osteogenic potential of MSC and that inhibition of WNT-5a signaling therefore plays a role in their determination into PA in humans.

Links

PubMed PMC2825412 Online version:10.1074/jbc.M109.054338

Keywords

Adipocytes/cytology; Adipogenesis; Cell Differentiation; Cell Lineage; Humans; Mesenchymal Stem Cells/cytology; Osteocytes/cytology; Osteogenesis; Proto-Oncogene Proteins/physiology; Wnt Proteins/physiology

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

MOUSE:WNT5A

acts_upstream_of

GO:0046330: positive regulation of JNK cascade

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:WNT5A

acts_upstream_of

GO:0043507: positive regulation of JUN kinase activity

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:WNT5A

involved_in

GO:0007257: activation of JUN kinase activity

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:WNT5A

involved_in

GO:0045778: positive regulation of ossification

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:WNT5A

involved_in

GO:0045599: negative regulation of fat cell differentiation

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:WNT5A

involved_in

GO:0038031: non-canonical Wnt signaling pathway via JNK cascade

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:WNT5A

involved_in

GO:0046330: positive regulation of JNK cascade

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete


See also

References

See Help:References for how to manage references in GONUTS.