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Discovered a new pathway regulating bone mass through gut and liver

A study with Spanish participation has described a new pathway that affects bone formation. The study, published by Journal of Clinical Investigation, opens new ways to therapeutic approaches for the first pathology associated with taurine deficiency.

UCC+i FICYT
9/6/2014 23:00 CEST

In blue, trabeculae (bone growing filaments within the bone). / Andrea Scauri

Researchers from the Wellcome Trust Sanger Institute in Cambridge with Spanish participation have detected a new pathway that determines bone creation. The paper, published today by the Journal of Clinical Investigation, opens new therapeutic perspectives.

Taurine is secreted in the liver through a process needing B12 vitamin, and stimulates bone growth and regeneration. It is what an international team of researchers have just proved with a study whose first authors are two young Spanish scientists.

When, with a fellowship from the ERA-EDTA Pablo Román García and Isabel Quirós González started to study in the Wellcome Trust Sanger Institute in Cambridge the effects of vitamine B12 lack, at the beginning they did not find anything remarkable. They were working over genetically modified mice in order to make their guts unable to absorb the vitamin.

Taurine is secreted in the liver through a process needing B12 vitamin, and stimulates bone growth and regeneration

“We were surprised to see how [those] mice didn’t show any anomaly, until we realized that, as concerning the most stable of all vitamins, the quantity they absorb during gestation is enough”, states Pablo Román García, first author of the paper and currently postdoctoral researcher at the Service of Bone and Mineral Metabolism of HUCA after a two-year stay at the British research centre.

By that time, Dr. Lynda Mottram and Arporn Wangwiwatsin from the systems biology of bone team discovered that genetically modified mice that lack the ability to absorb the vitamin B12 from their gut into the blood-stream were not able to grow and developed osteoporosis.

As they carried on the work, coordinated by Vijay K. Yadav, a senior author of the Sanger Institute, they started to harvest results: the second generation of mice, descendants of mothers unable to absorb B12 vitamin, grew scarcely and showed all the typical symptoms of osteoporosis. Taking into account that B12 is stored in the liver, researchers carried out metabollomics studies on the liver in collaboration with Dr. Vidya R. Velagapudi from the Institute for Molecular Medicine Finland (FIMM) in order to see what was occurring in B12 lacking livers: “We found several parameters altered, but the most significant was a very important alteration of taurine levels”, explains Pablo Román.

Two 'antidotes'

While they continued working on taurine, whose lack had not been associated with any pathology until now, researchers tried to revert the situation acting both on the mothers and on the mice unable to absorb B12 vitamin.

Results were revealing: “When injecting them with taurine, altered mice recovered their normal phenotype and therefore grew up normally and all the symptoms of osteoporosis disappeared”, underlines Pablo Román. The other way, focused on B12 vitamin, was equally effective, explains the Biochemist: “We reached the same results in the descendants by giving a single injection of the vitamin to the pregnant mothers”.

The lack of taurine had not been associated with any pathology until now

Taurine, the messenger of B12 on the bone

Taurine is a “quasi-amino acid” produced by the liver through a complex process involving vitamin B12. In fact, researchers directly proved that hepatic cells lacking B12 do not produce taurine. And while administering B12 directly onto bone cells does not produce any effect on them, as the research team proved, “when we administered taurine onto the bone cells we verified that consequently it increased the osteoblasts [bone creator cells] proliferation”.

With this work, researchers open new therapeutic approaches related to bone metabolism, although they specify that before a possible transfer to of these results to humans “many studies have to be done”.

Reference:
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, and Vijay K. Yadav, “Vitamine B12-dependent taurine synthesis regulates growth and bone mass”, The Journal of Clinical Investigation 2014; 124(7). Doi: 10.1172/JCI72606.

Source: JCI
Copyright: Creative Commons
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