Vitamin B12–dependent taurine synthesis regulates growth and bone mass
Pablo Roman-Garcia, … , Gordon Dougan, Vijay K. Yadav
Pablo Roman-Garcia, … , Gordon Dougan, Vijay K. Yadav
Published June 9, 2014
Citation Information: J Clin Invest. 2014;124(7):2988-3002. https://doi.org/10.1172/JCI72606.
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Research Article Bone Biology

Vitamin B12–dependent taurine synthesis regulates growth and bone mass

Abstract

Both maternal and offspring-derived factors contribute to lifelong growth and bone mass accrual, although the specific role of maternal deficiencies in the growth and bone mass of offspring is poorly understood. In the present study, we have shown that vitamin B12 (B12) deficiency in a murine genetic model results in severe postweaning growth retardation and osteoporosis, and the severity and time of onset of this phenotype in the offspring depends on the maternal genotype. Using integrated physiological and metabolomic analysis, we determined that B12 deficiency in the offspring decreases liver taurine production and associates with abrogation of a growth hormone/insulin-like growth factor 1 (GH/IGF1) axis. Taurine increased GH-dependent IGF1 synthesis in the liver, which subsequently enhanced osteoblast function, and in B12-deficient offspring, oral administration of taurine rescued their growth retardation and osteoporosis phenotypes. These results identify B12 as an essential vitamin that positively regulates postweaning growth and bone formation through taurine synthesis and suggests potential therapies to increase bone mass.

Authors

Pablo Roman-Garcia, Isabel Quiros-Gonzalez, Lynda Mottram, Liesbet Lieben, Kunal Sharan, Arporn Wangwiwatsin, Jose Tubio, Kirsty Lewis, Debbie Wilkinson, Balaji Santhanam, Nazan Sarper, Simon Clare, George S. Vassiliou, Vidya R. Velagapudi, Gordon Dougan, Vijay K. Yadav

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Figure 1

B12 deficiency in mice causes growth retardation and low bone mass.

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B12 deficiency in mice causes growth retardation and low bone mass. (A) ...
(A) Real-time PCR analysis of Gif expression in WT and Gif–/– tissues. (B) Serum B12 levels in WT, Gif–/–(F1), and Gif–/–(F2) mice. (C) BW analysis of WT, Gif–/–(F1) and Gif–/–(F2) mice. (D) Morphological analysis of 8-week-old WT, Gif–/–(F1), and Gif–/–(F2) mice. (E and F) Histological analysis of vertebrae (E) and μCT analysis of long bone (F) of WT, Gif–/–(F1), and Gif–/–(F2) mice. Mineralized bone matrix (black) was stained by von Kossa reagent. BV/TV, bone volume relative to total volume. Ct.Th., cortical thickness. (G) Toluidine blue staining showing reduced osteoblast number on bone surface, with quantification of Ob.N/T.Ar. (H) Photomicrographs showing near-absence of calcein double labeling on the surface of trabecular bone in Gif–/–(F2) mice, with quantification of BFR. (I) Photomicrographs showing TRAP-stained osteoclasts on the bone surface (pink), with quantification of osteoclast surface per bone surface (OcS/BS). #P < 0.05; *P < 0.01. Values are mean ± SEM. n = 8 [WT and Gif–/–(F2)]; 9 [Gif–/–(F2)]. Arrowheads on images indicate the location of cell types or parameters measured. Scale bars: 10 mm (D); 1 mm (E and F); 0.1 mm (G); 50 μm (H); 10 μm (H, insets); 0.05 mm (I). See also Supplemental Figure 1.