Secalciferol is a fat-soluble vitamin derived from plants and fungi, also known as (24R)-24,25-Dihydroxyvitamin D3. Secalciferol activates the vitamin D receptor (VDR) with an EC50 of 150nM[1-2]. Secalciferol is involved in various biological functions, including calcium homeostasis, cell differentiation, proliferation processes, and other functions related to the immune system. Secalciferol can be used in research on rickets, osteomalacia, hypercalcemia, and autoimmune diseases[3-4].
In vitro, Secalciferol (100pM - 10μM) was used to treat the IZ-VDRE and IZ-CYP24 stably transfected reporter gene cell lines for 24 hours. Secalciferol demonstrated a dose-dependent activation of the vitamin D receptor (VDR). The half-maximal effective concentration (EC50) of Secalciferol in the IZ-VDRE and IZ-CYP24 cell lines was 140.8nM and 166.1nM[5]. In the chondrogenic ATDC5 cell differentiation model, treatment with Secalciferol (0.1μM) for 7-14 days enhanced the gene expression of type 2 collagen (Col2a1) in Tlcd3b2-overexpressing cells, promoted proteoglycan synthesis, and facilitated the early differentiation of chondrocytes[6].
In vivo, Cyp24a1 knockout (Cyp24a1-/-) mice in a fracture repair model received subcutaneous injections of Secalciferol (6.7μg/kg/day) for 15 days. Secalciferol significantly corrected the defects in callus formation and callus stiffness during fracture repair in Cyp24a1-/- mice, restored callus volume, and improved the mechanical properties of the callus[7]. In hypophosphatemic (Hyp) mice, daily intraperitoneal injections of Secalciferol (1-1000μg/kg/day) for 28 days. Secalciferol significantly promoted bone formation in the lumbar vertebrae and improved bone formation parameters such as bone volume/tissue volume ratio and mineral apposition rate in a dose-dependent manner[8].
References:
[1] Henderson CM, Fink SL, Bassyouni H, et al. Vitamin D-Binding Protein Deficiency and Homozygous Deletion of the GC Gene. The New England Journal of Medicine. 2019 Mar;380(12):1150-1157.
[2] Wilson RT, Roff AN, Dai PJ, et al. Genetic Ancestry, Skin Reflectance and Pigmentation Genotypes in Association with Serum Vitamin D Metabolite Balance. Hormone Molecular Biology and Clinical Investigation. 2011 Sep;7(1):279-293.
[3] Makris K, Bhattoa HP, Cavalier E, et al. Recommendations on the measurement and the clinical use of vitamin D metabolites and vitamin D binding protein - A position paper from the IFCC Committee on bone metabolism. Clinica Chimica Acta; International Journal of Clinical Chemistry. 2021 Jun;517:171-197.
[4] Ikezaki S, Nishikawa A, Furukawa F, et al. Influences of long-term administration of 24R, 25-dihydroxyvitamin D3, a vitamin D3 derivative, in rats. J Toxicol Sci. 1999 May;24(2):133-9.
[5] Bartonkova I, Grycova A, Dvorak Z. Profiling of Vitamin D Metabolic Intermediates toward VDR Using Novel Stable Gene Reporter Cell Lines IZ-VDRE and IZ-CYP24. Chem Res Toxicol. 2016 Jul 18;29(7):1211-22.
[6] Antonyan L, Martineau C, St-Arnaud R. The ER protein TLC domain 3B2 and its enzymatic product lactosylceramide enhance chondrocyte maturation. Connect Tissue Res. 2021 Mar;62(2):176-182.
[7] Martineau C, Naja RP, Husseini A, et al. Optimal bone fracture repair requires 24R,25-dihydroxyvitamin D3 and its effector molecule FAM57B2. J Clin Invest. 2018 Aug 1;128(8):3546-3557.
[8] Ono T, Tanaka H, Yamate T, et al. 24R,25-dihydroxyvitamin D3 promotes bone formation without causing excessive resorption in hypophosphatemic mice. Endocrinology. 1996 Jun;137(6):2633-7.