Cindy Boer

32 | Chapter 1.2 Abstract Phenotypic variation in skeletal traits and diseases is the product of genetic and envi- ronmental factors. Epigenetic mechanisms include information‐containing factors, oth- er than DNA sequence, that cause stable changes in gene expression and are maintained during cell divisions. They represent a link between environmental influences, genome features, and the resulting phenotype. The main epigenetic factors are DNA methyl- ation, posttranslational changes of histones, and higher‐order chromatin structure. Sometimes non‐coding RNAs, such as microRNAs (miRNAs) and long non‐coding RNAs (lncRNAs), are also included in the broad term of epigenetic factors. There is rapidly expanding experimental evidence for a role of epigenetic factors in the differentiation of bone cells and the pathogenesis of skeletal disorders, such as osteoporosis and os- teoarthritis. However, different from genetic factors, epigenetic signatures are cell‐ and tissue‐specific and can change with time. Thus, elucidating their role has particular dif- ficulties, especially in human studies. Nevertheless, epigenome-wide association stud- ies are beginning to disclose some disease‐specific patterns that help to understand skeletal cell biology and may lead to development of new epigenetic‐based biomarkers, as well as new drug targets useful for treating diffuse and localized disorders. Here we provide an overview and update of recent advances on the role of epigenomics in bone and cartilage diseases.