Int J Med Sci 2021; 18(7):1580-1591. doi:10.7150/ijms.53650

Research Paper

The Role of Melanotransferrin (CD228) in the regulation of the differentiation of Human Bone Marrow-Derived Mesenchymal Stem Cells (hBM-MSC)

Maria Dubon1, Sooho Lee1, Ji-Hong Park1,2, Jae-Yong Lee3, Dongchul Kang1,2✉

1. Ilsong Institute of Life Science, Hallym University, Anyang, Gyeonggi-do 14066, Republic of Korea.
2. Department of Biomedical Gerontology, Graduate School of Hallym University, Chuncheon, Gangwon-do 24252, Republic of Korea.
3. Department of Biochemistry, College of Medicine, Hallym University, Chuncheon, Gangwon-do 24252, Republic of Korea.

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Citation:
Dubon M, Lee S, Park JH, Lee JY, Kang D. The Role of Melanotransferrin (CD228) in the regulation of the differentiation of Human Bone Marrow-Derived Mesenchymal Stem Cells (hBM-MSC). Int J Med Sci 2021; 18(7):1580-1591. doi:10.7150/ijms.53650. Available from https://www.medsci.org/v18p1580.htm

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Abstract

Melanotransferrin (CD228), firstly reported as a melanoma-associated antigen, is a membrane-bound glycoprotein of an iron-binding transferrin homolog. CD228 was found to be expressed significantly higher in human bone marrow-derived mesenchymal stem cells (hBM-MSC) than in human embryonic fibroblasts (FB) by RT-PCR, western blotting and flow cytometry. The expression of CD228 declined in aged hBM-MSC as osteogenesis-related genes did. We examined a possible role for CD228 in the regulation of osteogenesis and adipogenesis of hBM-MSC. Surprisingly, siRNA-mediated CD228 knockdown increased the expression of the transcription factor DLX5 and enhanced osteogenesis of hBM-MSC evidenced by an increased expression of the runt-related transcription factor 2 (RUNX2), osterix (Osx), and osteocalcin (OC), as well as higher alkaline phosphatase (ALP) activity and extracellular calcium deposition. Interestingly, hBM-MSC transfected with CD228 siRNA also showed an increase in intracellular lipid level during adipogenesis, indicated by oil red O staining of differentiated adipocytes. Overall, our study unveils CD228 as a cell surface molecule expressed by young hBM-MSC, but not by FB. It also provides evidence to suggest a role for CD228 as a negative regulator of osteogenesis and of lipid accumulation during adipogenesis in hBM-MSC in vitro.

Keywords: Melanotransferrin, differentiation, osteogenesis, adipogenesis, mesenchymal stem cells, cell surface markers