Novel biological process regulating growth and bone cell formation identified
An international research group has identified a novel biological process that regulates the production of new bone cells. This pathway involves vitamin B12 but also taurine, a poorly understood amino acid synthesized in the liver.
The aim of the researchers was to get more information about the role of vitamin B12 in the regulation of growth. For this, the researchers created a mouse model of B12 deficiency by deleting a gene called Gastric Intrinsic Factor gene, Gif, which is expressed in the stomach and essential for B12 absorption from the gut. Using this mouse model, it was possible to study both maternal and offspring-related factors.
The B12 deficient mice had growth retardation and low bone mass at eight weeks of age. Interestingly, the effects of B12 deficiency were shown to be mediated by downstream signaling of the hypothalamic/pituitary growth hormone axis. This led to the identification of taurine as a metabolite regulated by B12 and underlying the growth retardation in B12-deficient offspring. When B12 deficient animals were treated with taurine, their growth retardation phenotype was completely rescued. Similarly, a single injection of vitamin B12 during pregnancy was enough to prevent the symptoms in the offspring.
In addition to the mouse model, the study contained data from two different sets of human patients providing further support for the role of vitamin B12. Samples from Turkish children born of nutritionally vitamin B12-deficient mothers showed a significant decrease in levels of vitamin B12 and taurine. In addition, samples of older patients with vitamin B12 deficiency from the Kuopio Ischaemic Heart Disease Risk Factor Study (KIHD study) confirmed the correlation between B12 and taurine levels.
The role of Adjunct Professor Vidya Velagapudi, Head of FIMM’s Metabolomic Unit, was to supervise all the metabolomic measurements, data analysis and coordinate all the clinical studies.
-These surprising results identifying B12 vitamin as an essential regulator of growth and bone formation as well as proving that taurine production has an important role open completely new ways of thinking and could offer potential new targets for osteoporosis treatment, she says.
-Since the human studies performed thus far had a small sample size and concentrated on B12 deficient patients, further studies confirming the connection between vitamin B12, taurine and bone formation in general populations are needed/underway.
Vitamin B12-dependent taurine synthesis regulates growth and bone mass.
Roman-Garcia P, Quiros-Gonzalez I, Mottram L, Lieben L, Sharan K, Wangwiwatsin A, Tubio J, Lewis K, Wilkinson D, Santhanam B, Sarper N, Clare S, Vassiliou GS, Velagapudi VR, Dougan G, Yadav VK.
J Clin Invest. 2014 Jun 9. pii: 72606. doi: 10.1172/JCI72606. [Epub ahead of print]
Read more: Sanger Press Release