Department of Pharmaceutical Engineering, Faculty of Engineering, Toyama Prefectural University, 5180 Kurokawa, Imizu, Toyama, 939-0398, Japan.
Department of Food and Nutrition, Okayama Gakuin University, 787 Aruki, Kurashiki, Okayama, 710-8511, Japan.
Sci Rep. 2023 Oct 28;13(1):18528. doi: 10.1038/s41598-023-45594-2.
Type II rickets is a hereditary disease caused by a mutation in the vitamin D receptor (VDR) gene. The main symptoms of this disease are bone dysplasia and alopecia. Bone dysplasia can be ameliorated by high calcium intake; however, there is no suitable treatment for alopecia. In this study, we verified whether gene therapy using an adenoviral vector (AdV) had a therapeutic effect on alopecia in Vdr-KO rats. The VDR-expressing AdV was injected into six 7-week-old female Vdr-KO rats (VDR-AdV rats). On the other hand, control-AdV was injected into 7-week-old female rats (control-AdV rats); non-infected Vdr-KO rats (control rats) were also examined. The hair on the backs of the rats was shaved with hair clippers, and VDR-AdV or control-AdV was intradermally injected. Part of the back skin was collected from each rat after AdV administration. Hair follicles were observed using hematoxylin and eosin staining, and VDR expression was examined using immunostaining and western blotting. VDR-AdV rats showed significant VDR expression in the skin, enhanced hair growth, and low cyst formation, whereas control-AdV and non-infected rats did not show any of these effects. The effect of VDR-AdV lasted for nearly 60 days. These results indicate that gene therapy using VDR-AdV may be useful to treat alopecia associated with type II rickets, if multiple injections are possible after a sufficient period of time.
Ⅱ型佝偻病是一种遗传性疾病，由维生素 D 受体（VDR）基因突变引起。该病的主要症状为骨骼发育不良和脱发。高钙摄入可改善骨骼发育不良，但对脱发尚无合适的治疗方法。本研究旨在验证腺病毒载体（AdV）基因治疗对 Vdr-KO 大鼠脱发的疗效。将表达 VDR 的 AdV 注入 6 只 7 周龄雌性 Vdr-KO 大鼠（VDR-AdV 大鼠）体内。另一方面，将对照 AdV 注入 7 周龄雌性大鼠（对照 AdV 大鼠），并对未感染 Vdr-KO 大鼠（对照大鼠）进行了检查。用理发推子将大鼠背部的毛发剃光，然后皮内注射 VDR-AdV 或对照 AdV。AdV 给药后从每只大鼠采集部分背部皮肤。用苏木精-伊红染色观察毛囊，用免疫染色和 Western blot 检测 VDR 表达。VDR-AdV 大鼠皮肤中 VDR 表达明显，毛发生长增强，囊泡形成减少，而对照 AdV 和未感染大鼠则没有这些作用。VDR-AdV 的作用持续了近 60 天。这些结果表明，如果可以在足够长的时间后进行多次注射，VDR-AdV 基因治疗可能对治疗与Ⅱ型佝偻病相关的脱发有用。
