Int J Biol Sci 2022; 18(14):5391-5404. doi:10.7150/ijbs.73673 This issue Cite

Research Paper

Vitamin D Promotes Remyelination by Suppressing c-Myc and Inducing Oligodendrocyte Precursor Cell Differentiation after Traumatic Spinal Cord Injury

Ning Li1,2, Min Yao1,3, Jiaxin Liu1, Zhiyuan Zhu1,4, Tsz-Lung Lam1, Pingde Zhang1, Karrie Mei-Yee Kiang1✉, Gilberto Ka-Kit Leung1✉

1. Department of Surgery, School of Clinical Medicine, LKS Faculty of Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong.
2. Department of Neurosurgery, Zhongda Hospital, Southeast University, Nanjing, China.
3. School of Pharmaceutical Sciences, Health Science Centre, Shenzhen University, Shenzhen, China.
4. Department of Functional Neurosurgery, Zhujiang Hospital, Southern Medical University, Guangzhou, China.

Citation:
Li N, Yao M, Liu J, Zhu Z, Lam TL, Zhang P, Kiang KMY, Leung GKK. Vitamin D Promotes Remyelination by Suppressing c-Myc and Inducing Oligodendrocyte Precursor Cell Differentiation after Traumatic Spinal Cord Injury. Int J Biol Sci 2022; 18(14):5391-5404. doi:10.7150/ijbs.73673. https://www.ijbs.com/v18p5391.htm
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Abstract

Graphic abstract

Demyelination due to oligodendrocytes loss occurs after traumatic spinal cord injury (TSCI). Several studies have suggested the therapeutic potential of vitamin D (VitD) in demyelinating diseases. However, experimental evidence in the context of TSCI is limited, particularly in the presence of prior VitD-deficiency. In the present study, a contusion and a transection TSCI rat model were used, representing mild and severe injury, respectively. Motor recovery was assessed in rats with normal VitD level or with VitD-deficiency after 8 weeks' treatment post-TSCI (Cholecalciferol, 500 IU/kg/day). The impact on myelin integrity was examined by transmission electron microscopy and studied in vitro using primary culture of oligodendrocytes. We found that VitD treatment post-TSCI effectively improved hindlimb movement in rats with normal VitD level irrespective of injury severity. However, cord-transected rats with prior deficiency did not seem to benefit from VitD supplementation. Our data further suggested that having sufficient VitD was essential for persevering myelin integrity after injury. VitD rescued oligodendrocytes from apoptotic cell death in vitro and enhanced their myelinating ability towards dorsal root axons. Enhanced myelination was mediated by increased oligodendrocyte precursor cells (OPCs) differentiation into oligodendrocytes in concert with c-Myc downregulation and suppressed OPCs proliferation. Our study provides novel insights into the functioning of VitD as a regulator of OPCs differentiation as well as strong preclinical evidence supporting future clinical testing of VitD for TSCI.

Keywords: Vitamin D, Myelination, Spinal cord injury, Oligodendrocyte, Differentiation


Citation styles

APA
Li, N., Yao, M., Liu, J., Zhu, Z., Lam, T.L., Zhang, P., Kiang, K.M.Y., Leung, G.K.K. (2022). Vitamin D Promotes Remyelination by Suppressing c-Myc and Inducing Oligodendrocyte Precursor Cell Differentiation after Traumatic Spinal Cord Injury. International Journal of Biological Sciences, 18(14), 5391-5404. https://doi.org/10.7150/ijbs.73673.

ACS
Li, N.; Yao, M.; Liu, J.; Zhu, Z.; Lam, T.L.; Zhang, P.; Kiang, K.M.Y.; Leung, G.K.K. Vitamin D Promotes Remyelination by Suppressing c-Myc and Inducing Oligodendrocyte Precursor Cell Differentiation after Traumatic Spinal Cord Injury. Int. J. Biol. Sci. 2022, 18 (14), 5391-5404. DOI: 10.7150/ijbs.73673.

NLM
Li N, Yao M, Liu J, Zhu Z, Lam TL, Zhang P, Kiang KMY, Leung GKK. Vitamin D Promotes Remyelination by Suppressing c-Myc and Inducing Oligodendrocyte Precursor Cell Differentiation after Traumatic Spinal Cord Injury. Int J Biol Sci 2022; 18(14):5391-5404. doi:10.7150/ijbs.73673. https://www.ijbs.com/v18p5391.htm

CSE
Li N, Yao M, Liu J, Zhu Z, Lam TL, Zhang P, Kiang KMY, Leung GKK. 2022. Vitamin D Promotes Remyelination by Suppressing c-Myc and Inducing Oligodendrocyte Precursor Cell Differentiation after Traumatic Spinal Cord Injury. Int J Biol Sci. 18(14):5391-5404.

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