Cellular retinol-binding protein 1 (CRBP-1) regulates osteogenenesis and adipogenesis of mesenchymal stem cells through inhibiting RXRα-induced β-catenin degradation.
Mesenchymal stem cells (MSCs) are multipotent adult stem cells that can differentiate into osteoblasts, chondrocytes and adipocytes, providing a potential source for musculoskeletal tissue engineering. Retinoid signaling plays very important roles in skeletal development. CRBP1 (cellular retinol binding protein 1), a key component of retinoid signaling pathway, is known to take part in vitamin A metabolism and intracellular transporting of retinoids. However, the role of CRBP1 in MSCs remains still obscure. In this study, we investigated the cellular effects of CRBP1 on osteogenic and adipogenic differentiation of bone marrow derived MSCs in vitro and in vivo. Our results showed that CRBP1 overexpression promoted osteogenic differentiation of bone marrow derived MSCs, while inhibited their adipogenic differentiation. We also demonstrated that the possible underlying mechanism for CRBP1 promoting osteogenic differentiation of MSCs was by inhibiting RXRα-induced β-catenin degradation, maintaining β-catenin and pERK1/2 at higher levels. These findings reveal a potential role of CRBP1 in the regulation of β-catenin turnover which can greatly affect the process of osteogenesis and adipogenesis of MSCs.
Stem Cells and Regeneration Program, School of Biomedical Sciences, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong, China.
Liangliang
L
Xu
Chao
C
Song
Ming
M
Ni
Fanbiao
F
Meng
Huiqi
H
Xie
Gang
G
Li
D050156:Adipogenesis; D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology; D020868:Gene Silencing; D057809:HEK293 Cells; D006801:Humans; D016086:Lentivirus / Q000235:genetics; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000378:metabolism*; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D010012:Osteogenesis; D010750:Phosphoproteins / Q000378:metabolism; D055550:Protein Stability; D059748:Proteolysis; D034741:RNA, Small Interfering / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D047490:Retinoid X Receptor alpha / Q000378:metabolism*; D054840:Retinol-Binding Proteins, Cellular / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D051176:beta Catenin / Q000378:metabolism*
D010750:Phosphoproteins; D034741:RNA, Small Interfering; D047490:Retinoid X Receptor alpha; D054840:Retinol-Binding Proteins, Cellular; D051176:beta Catenin; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3