25 February 2019

Too much vitamin D and excessive macrophages stimulate the development of myelofibrosis, a Japanese study in mice has discovered.

The research team from Kobe University in Japan hopes the findings could pave the way for the development of new treatments for myeloproliferative neoplasms (MPNs) with myelofibrosis.

The research team, led by research fellow Kanako Wakahashi and junior associate professor Yoshio Katayama, focused on the relationship between blood and bone.

Using a mouse model of myelofibrosis, they found that vitamin D signalling induced the differentiation of haematopoietic stem cells into macrophages, which in turn stimulated young osteoblasts to induce myelofibrosis and bone hardening.

The team was able to largely prevent the onset of myelofibrosis by giving the mice a low vitamin D diet or by removing macrophages from the bone marrow.

The team also examined mouse models with the same genetic disorder that many MPN patients carry (JAK2V61F transgenic mice) and they were found to have similar symptoms to myelofibrosis patients.

Giving these MPN mice a low vitamin D diet, blocking vitamin D receptor signalling, and removing macrophages, also proved to be an effective method of preventing bone marrow fibrosis.

Professor Katayama said: “The only permanent cure for this disease is haematopoietic stem cell transplant, but this method is unsuitable for many elderly patients. These new findings may help to develop a treatment method for the elderly targeting the vitamin D pathway and macrophages.”

Source: Wakahashi, K., Minagawa, K., Kawano, Y., Kawano, H., Suzuki, T., Ishii, S., Sada, A., Asada, N., Sato, M., Kato, S., Shide, K., Shimoda, K., Matsui, T., Katayama, Y. (2019) “Vitamin D receptor-mediated skewed differentiation of macrophages initiates myelofibrosis and subsequent osteosclerosis”, Blood, available via doi: 10.1182/blood-2018-09-876615


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