-6396/12 www.nature.com/bonekey
IntroductionEukaryotic cells are characterized by a compartmentation structure that divides the intracellular space in two different regions, the nucleus and the cytoplasm. 1 This compartmentation is maintained by the nuclear envelope, which is a perinuclear cisterna of the endomembrane system and is constituted by the inner nuclear membrane (INM) and the outer nuclear membrane (ONM) enclosing a lumen ( ' perinuclear space ' ) ( Figure 1 ). The integrity of this structure is interrupted by the nuclear pore complexes (NPC), which span both the inner and the outer membranes and are the portal between the nucleus and the cytoplasm. 1 -3 Owing to the continuity between the nuclear envelope and the endoplasmic reticulum, the main functions of the ONM are very similar to those of the endoplasmic reticulum. 4 In contrast, the INM is in close interaction with the nuclear lamina, multiple nuclear proteins and chromosomes, 2 having an essential role in cell differentiation, organization of chromatin and communication with the extranuclear cytoskeleton. 2,5 Recent evidence has emerged demonstrating that the nuclear lamina, a network of intermediate filament proteins, 6 is not only closely associated with the INM ( Figure 1 ) but is also an important determinant of its function and interactions.The intermediate filament proteins that compose the nuclear lamina are known as lamins, 5,6 the lamin gene family in mammals includes three different genes that encode seven different proteins (lamin A, A 10, C, C2, B1, B2 and B3). Most adult mammalian somatic cells contain the three major lamins A, B1 and C. These various forms are grouped into two classes, A-type (A, A 10 and C) and B-type (B1 and B2). Although B-type lamins are found in all nucleated somatic cells, the expression of A-type lamins is developmentally regulated.A-type lamins have been recently linked to a number of human progeroid syndromes and adult-onset degenerative diseases; 6 -8 therefore, in this review we will focus on the role of A-type lamins in bone cells particularly in the age-related changes that predispose to osteoporosis and fractures. By reviewing this evidence, we will propose that modulating the expression of A-type lamins in the musculoskeletal system could become a new therapeutic intervention to prevent age-related bone loss and osteoporosis.
Age-related Bone Loss and OsteoporosisWith increasing age, there is a significant reduction in bone formation. This is mostly due to a shift from osteoblastogenesis to
REVIEWRole of the nuclear envelope in the pathogenesis of age-related bone loss and osteoporosis The nuclear envelope is the most important border in the eukaryotic cell. The role of the nuclear envelope in cell differentiation and function is determined by a constant interaction between the elements of the nuclear envelope and the transcriptional regulators involved in signal transcription pathways. Among those components of the nuclear envelope, there is a growing evidence that changes in the expression of A...