Structural maintenance of chromosome complexes and bone development: the beginning of a wonderful relationship?

Bone development depends on environmental, nutritional and hormonal factors. Yet, an ordered and timed activation of genes and their associated molecular pathways are central for the growth and development of healthy bones. The correct expression of genes depends on both cis- and trans-regulatory elements. Of these, the elusive role of chromatin ultrastructure is just beginning to become appreciated. Changes in the higher-order structure of chromatin are affecting the expression of genes in response to intrinsic and environmental signals. Cohesin and condensin are members of the structural maintenance of chromosome (SMC) family of protein complexes, which mediate higher-order chromatin structure by tethering distinct regions of chromatin either inter- or intra-molecularly. In recent years, SMCs had been identified for their function in the regulation of gene expression and developmental processes, whereas malfunction of cohesin or condensin has an impact on human health. However, little is known about the specific roles of SMC complexes in bone development and their possible effect on bone health. Here, we review studies that suggest an intimate link between SMCs and bone development, as well as a plausible effect, direct or indirect, on the bone health. We describe genetic syndromes associated with SMCs with distinctive bone phenotypes and identify links between SMCs and bone-related molecular pathways. Future studies of the relationship between SMCs and bone development will reveal new understandings of both the cellular and molecular roles of SMC complexes and provide new insights into the growth and developmental processes in the bone.