Memories from a different past: role of epigenetics in the cell biology of sclerostin deficiency

Background: Epigenetic changes are heritable modifications in gene expression without alterations in DNA sequences.

It is well established that epigenetic remodelling is associated with disease and aging, but it now emerging that epigenetics may also mediate memory of tissue-forming responses and immunological insult. Indeed, it has recently been shown that modification of DNA methylation following a single anabolic stimulus is responsible for muscle hypertrophy (growth) and that a 'memory' of this event is maintained for a long period (over 5 months; 1).

Additionally, innate immune memory of macrophages potentially occurs in both circulating and tissue-resident cells with epigenetic modifications most likely to mediate this phenomenon(2). We have discovered that skeletal cells display memory when extracted from a skeleton functioning under constant anabolic signalling (sclerostin deficiency), and speculate that this is governed epigenetically.