the role of dna methylation in common skeletal disordersdna甲基化作用的常见的骨骼疾病.pdfVIP

Biology 2012, 1, 698-713; doi:10.3390/biology1030698 OPEN ACCESS biology ISSN 2079-7737 /journal/biology Review The Role of DNA Methylation in Common Skeletal Disorders Jesús Delgado-Calle and José A. Riancho * Department of Internal Medicine, H.U. Marqués de Valdecilla-IFIMAV-University of Cantabria, Santander 39008, Spain; E-Mail: jesusdelgadocalle@ * Author to whom correspondence should be addressed; E-Mail: rianchoj@unican.es; Tel.: +34-942-201-990; Fax: +34-942-201-695. Received: 25 September 2012; in revised form: 31 October 2012 / Accepted: 16 November 2012 / Published: 22 November 2012 Abstract : Bone is a complex connective tissue characterized by a calcified extracellular matrix. This mineralized matrix is constantly being formed and resorbed throughout life, allowing the bone to adapt to daily mechanical loads and maintain skeletal properties and composition. The imbalance between bone formation and bone resorption leads to changes in bone mass. This is the case of osteoporosis and osteoarthritis, two common skeletal disorders. While osteoporosis is characterized by a decreased bone mass and, consequently, higher susceptibly to fractures, bone mass tends to be higher in patients with osteoarthritis, especially in the subchondral bone region. It is known that these diseases are influenced by heritable factors. However, the DNA polymorphisms identified so far in GWAS explain less than 10% of the genetic risk, suggesting th