Next Article in Journal
Acteoside and Isoacteoside Protect Amyloid β Peptide Induced Cytotoxicity, Cognitive Deficit and Neurochemical Disturbances In Vitro and In Vivo
Next Article in Special Issue
Decrease of miR-195 Promotes Chondrocytes Proliferation and Maintenance of Chondrogenic Phenotype via Targeting FGF-18 Pathway
Previous Article in Journal
CoQ10 Deficiency May Indicate Mitochondrial Dysfunction in Cr(VI) Toxicity
Previous Article in Special Issue
A Pronounced Inflammatory Activity Characterizes the Early Fracture Healing Phase in Immunologically Restricted Patients
Article Menu
Issue 4 (April) cover image

Export Article

Open AccessArticle
Int. J. Mol. Sci. 2017, 18(4), 880; doi:10.3390/ijms18040880

Role of RHEB in Regulating Differentiation Fate of Mesenchymal Stem Cells for Cartilage and Bone Regeneration

Department of Biomedical Science, CHA University, Seongnam-si 463-400, Korea
School of Integrative Engineering, Chung-Ang University, Seoul 156-863, Korea
Department of Neurosurgery, Bundang Medical Center, CHA University, Seongnam-si 463-400, Korea
Authors to whom correspondence should be addressed.
Academic Editor: Cory J. Xian
Received: 19 February 2017 / Revised: 18 April 2017 / Accepted: 19 April 2017 / Published: 24 April 2017
(This article belongs to the Special Issue Advances in Bone and Cartilage Research)
View Full-Text   |   Download PDF [3573 KB, uploaded 24 April 2017]   |  


Advances in mesenchymal stem cells (MSCs) and cell replacement therapies are promising approaches to treat cartilage and bone defects since substantial differentiation capacities of MSCs match the demands of tissue regeneration. Our understanding of the dynamic process requiring indispensable differentiation of MSCs remains limited. Herein, we describe the role of RHEB (Ras homolog enriched in brain) regulating gene signature for differentiation of human adipose derived mesenchymal stem cells (ASCs) into chondrogenic, osteogenic, and adipogenic lineages. RHEB-overexpression increases the proliferation of the ASCs. RHEB enhances the chondrogenic differentiation of ASCs in 3D culture via upregulation of SOX9 with concomitant increase in glycosaminoglycans (GAGs), and type II collagen (COL2). RHEB increases the osteogenesis via upregulation of runt related transcription factor 2 (RUNX2) with an increase in the calcium and phosphate contents. RHEB also increases the expression of osteogenic markers, osteonectin and osteopontin. RHEB knockdown ASCs were incapable of expressing sufficient SRY (Sex determining region Y)-box 9 (SOX9) and RUNX2, and therefore had decreased chondrogenic and osteogenic differentiation. RHEB-overexpression impaired ASCs differentiation into adipogenic lineage, through downregulation of CCAAT/enhancer binding protein beta (C/EBPβ). Conversely, RHEB knockdown abolished the negative regulation of adipogenesis. We demonstrate that RHEB is a novel regulator, with a critical role in ASCs lineage determination, and RHEB-modulated ASCs may be useful as a cell therapy for cartilage and bone defect treatments. View Full-Text
Keywords: mesenchymal stem cells; Ras homolog enriched in brain (RHEB); differentiation; chondrogenesis; osteogenesis; adipogenesis mesenchymal stem cells; Ras homolog enriched in brain (RHEB); differentiation; chondrogenesis; osteogenesis; adipogenesis

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

Supplementary material

Scifeed alert for new publications

Never miss any articles matching your research from any publisher
  • Get alerts for new papers matching your research
  • Find out the new papers from selected authors
  • Updated daily for 49'000+ journals and 6000+ publishers
  • Define your Scifeed now

SciFeed Share & Cite This Article

MDPI and ACS Style

Ashraf, S.; Han, I.-B.; Park, H.; Lee, S.-H. Role of RHEB in Regulating Differentiation Fate of Mesenchymal Stem Cells for Cartilage and Bone Regeneration. Int. J. Mol. Sci. 2017, 18, 880.

Show more citation formats Show less citations formats

Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Related Articles

Article Metrics

Article Access Statistics



[Return to top]
Int. J. Mol. Sci. EISSN 1422-0067 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top