Background: Differentiating oligodendrocyte precursor cells (OPCs) into oligodendrocytes could be improved by inhibiting signaling pathways such as Wnt and Notch. 9-cis-retinoic acid (9-cis-RA) and 1,25-dihydroxyvitamin D3 (1,25[OH]2D3) can ameliorate oligodendrogenesis. We investigated whether they could increase oligodendrogenesis by inhibiting the Wnt and Notch signaling pathways.
Methods: Cortical neural stem cells were isolated from 14-day-old rat embryos and cultured using the neurosphere assay. The cells were treated in 4 different conditions for 1 week: the negative control group received only the basic fibroblast growth factor, the positive control group received only T3 without growth factors, the RA group was treated with 9-cis-RA, and the Vit D3 group was treated with 1,25(OH)2D3. The effects of 9-cis-RA and 1,25(OH)2D3 on the level of the myelin basic protein (MBP) and the gene expression of the SOX10, MBP gene, HES5, and LRP6 were studied using flow cytometry and real-time PCR. The data were analyzed using one-way ANOVA with GraphPad Prism. A P value less than 0.05 was considered significant.
Results: The mRNA expressions of the SOX10, MBP, and MBP gene were significantly increased in the treated groups compared with the negative control group; the increase was similar in the 9-cis-RA group and the positive control group. Furthermore, 9-cis-RA significantly decreased the expression of the HES5 gene, a Notch signaling pathway transcription factor, and 1,25(OH)2D3 significantly reduced the expression of the LRP6 gene, a Wnt signaling pathway co-receptor.
Conclusion: It seems that 9-cis-RA and 1,25(OH)2D3 are good candidates to improve the differentiation of OPCs into oligodendrocytes.
Keywords: 1,25-dihydroxy vitamin D3; 9-cis-retinoic acid; Notch signaling pathway; Oligodendrocyte precursor cells; Receptors, Wnt; Cell differentiation.
Induction of androgen receptor by 1alpha,25-dihydroxyvitamin D3 and 9-cis retinoic acid in LNCaP human prostate cancer cells.Endocrinology. 1999 Mar;140(3):1205-12. doi: 10.1210/endo.140.3.6561. Endocrinology. 1999. PMID: 10067845
Antiproliferative responses to two human colon cancer cell lines to vitamin D3 are differently modified by 9-cis-retinoic acid.Cancer Res. 1996 Feb 1;56(3):623-32. Cancer Res. 1996. PMID: 8564982
1,25-Dihydroxyvitamin D3 induces differentiation of a retinoic acid-resistant acute promyelocytic leukemia cell line (UF-1) associated with expression of p21(WAF1/CIP1) and p27(KIP1).Blood. 1999 Apr 1;93(7):2225-33. Blood. 1999. PMID: 10090931
Combination of a potent 20-epi-vitamin D3 analogue (KH 1060) with 9-cis-retinoic acid irreversibly inhibits clonal growth, decreases bcl-2 expression, and induces apoptosis in HL-60 leukemic cells.Cancer Res. 1996 Aug 1;56(15):3570-6. Cancer Res. 1996. PMID: 8758928
The vitamin D hormone and its nuclear receptor: molecular actions and disease states.J Endocrinol. 1997 Sep;154 Suppl:S57-73. J Endocrinol. 1997. PMID: 9379138 Review.
Cited by 1 article
Transplantation of NSCs Promotes the Recovery of Cognitive Functions by Regulating Neurotransmitters in Rats with Traumatic Brain Injury.Neurochem Res. 2019 Dec;44(12):2765-2775. doi: 10.1007/s11064-019-02897-z. Epub 2019 Nov 7. Neurochem Res. 2019. PMID: 31701381