Mechanisms of bone formation by primary cilia

Abstract

Primary cilia are immotile cilia assembled from the centriole-derived basal body, and they protrude on the cell surface in almost all cell types during the cell cycle G0 phase. Due to the diffusion barrier at the ciliary base, cilia harbor selective G protein-coupled receptors, growth factor receptors, and ion channels on their membrane. Thus, cilia act as sensory organelles, regulating the proliferation and differentiation of the cells and promoting the formation and maturation of various organs including bone, brain, and kidney. It has been unveiled that malformation and dysregulation of cilia cause organ dysplasia, so-called ciliopathy, thus research on primary cilia has become active during the past 20 years. Research on the roles of cilia in bone formation and its regulatory mechanisms have also progressed. It is widely recognized that cilia of preosteoblasts receive hedgehog and promote differentiation of the cells to osteoblasts, resulting in the formation of skulls and long bones. Recently, it has been shown that a membrane-associated protein 4.1G is important in ciliogenesis, hedgehog signaling, and osteoblast differentiation in neonatal bone formation. In this review, we would like to summarize the roles of primary cilia in bone formation and their regulatory mechanisms including the contribution of 4.1G.