The osteogenic or adipogenic lineage commitment of human mesenchymal stem cells is determined by protein kinase C delta

BMC Cell Biology

Research Article

Sooho Lee¹  Hee-Yeon Cho²  Hang Thi Thuy Bui²  Dongchul Kang² 

[1] Ilsong Institute of Life Science, Hallym University, 431-060, Gyeonggi-do, Anyang, Republic of Korea;Ilsong Institute of Life Science, Hallym University, 431-060, Gyeonggi-do, Anyang, Republic of Korea;Department of Biomedical Gerontology, Graduate School of Hallym University, 200-702, Gangwon-do, Chuncheon, Republic of Korea;

关键词: hBMSCs;    Osteogenic differentiation;    Signal transduction;    PKCδ;    AMPK;   

DOI  :  10.1186/s12860-014-0042-4

 received in 2014-07-10, accepted in 2014-11-05,  发布年份 2014

来源: Springer

【 摘 要 】

BackgroundMesenchymal stem cells (MSCs) have the potential to differentiate into specialized cell lineages such as osteoblasts and adipocytes in vitro. There exists a reciprocal relationship between osteogenic and adipogenic differentiation of MSCs that an osteogenic phenotype occurs at the expense of an adipogenic phenotype and vice versa, which in turn influence one another's phenotype through negative feedback loops. Thus, it is important to understand what signaling molecules modulate the lineage commitment of MSCs. Protein kinase C (PKC) plays a central role in cellular signal transduction for mediating diverse biological functions, and dysregulation of PKC activity is involved in various metabolic diseases including cancer, diabetes, and heart disease. Although the role of individual PKC isoforms has been investigated in various fields, the potential role of PKC in bone metabolism is not completely understood. In this study, we investigated the potential role of PKCδ in osteogenic lineage commitment of human bone marrow-derived mesenchymal stem cells (hBMSCs).ResultsWe observed that expression and phosphorylation of PKCδ were increased during osteogenic differentiation of hBMSCs. Pharmacological inhibition and genetic ablation of PKCδ in hBMSCs resulted in a significant attenuation of osteogenic differentiation as evidenced by reduced ALP activity and ECM mineralization, as well as down-regulation of the expression of osteoblast-specific genes. These effects were also accompanied by induction of adipogenic differentiation and up-regulation of the expression of adipocyte-specific genes involved in lipid synthesis in osteogenic induction of hBMSCs. Additionally, the activation of AMPK, which is a key cellular energy sensor, induced osteogenesis of hBMSCs. However, the inhibition of AMPK activity by compound C did not affect the activation of PKCδ at all, indicating that there is no direct correlation between AMPK and PKCδ in osteogenesis of hBMSCs.ConclusionsThese results suggest that PKCδ is a critical regulator for the balance between osteogenesis and adipogenesis of hBMSCs and thus has a potential novel therapeutic target for the treatment of metabolic bone diseases.

【 授权许可】

Unknown   
© Lee et al.; licensee BioMed Central Ltd. 2014. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.