Ribosome biogenesis in skeletal development and the pathogenesis of skeletal disorders

Abstract

The skeleton affords a framework and structural support for vertebrates, while also facilitating movement, protecting vital organs, and providing a reservoir of minerals and cells for immune system and vascular homeostasis. The mechanical and biological functions of the skeleton are inextricably linked to the size and shape of individual bones, the diversity of which is dependent in part upon differential growth and proliferation. Perturbation of bone development, growth and proliferation, can result in congenital skeletal anomalies, which affect approximately 1 in 3000 live births [1]. Ribosome biogenesis is integral to all cell growth and proliferation through its roles in translating mRNAs and building proteins. Disruption of any steps in the process of ribosome biogenesis can lead to congenital disorders termed ribosomopathies. In this review, we discuss the role of ribosome biogenesis in skeletal development and in the pathogenesis of congenital skeletal anomalies. This article is part of a Special Issue entitled: Role of the Nucleolus in Human Disease.

Keywords: Cartilage hair hypoplasia; Ribosome biogenesis; Roberts syndrome; Shwachman–Diamond syndrome; Skeletal development; Treacher Collins syndrome.

Figure 1

Schematic diagram summarizing of the major components of ribosome biogenesis and the intersection of specific genes that lead to the pathogenesis of distinct ribosomopathies.

Figure 2

Skeletal development proceeds either through endochondral or intramembranous ossification. This schema of the stratified growth plate in a long bone depicts the transition of the chondroprogenitor cell through the developmental progression of endochondral ossification, which includes proliferation, maturation, hypertrophy and ultimately cell death. Osteoprogenitor cells then invade the void left by hypertrophy, differentiate into osteoblasts, and maturate into osteocytes. Differentiation and maturation of osteoprogenitor cells is indistinguishable between endochondral and intramembranous ossification.