Functional Diversity of Ciliary Proteins in Bone Development and Disease

The primary cilium is a non-motile microtubule-based organelle that senses a diverse range of extracellular signals. While recent studies highlight the importance of ciliary-dependent developmental signals, including Hedgehog, Wnt, and platelet-derived growth factor, it is not well understood whether and how bone morphogenetic protein (BMP) signaling, a key regulator of skeletogenesis, is involved in cilia-related bone developmental aspects and in the etiology of skeletal disorders.

Increasing evidence suggests that osteoblast- or osteocyte-specific deletion of ciliary proteins leads to diverse skeletal malformations, reinforcing the idea that primary cilia are indispensable for regulating bone development and maintenance. Furthermore, it became evident that ciliary proteins not only contribute to ciliogenesis but also orchestrate cellular trafficking. This review summarizes the current understanding of ciliary proteins in bone development and discusses the potential role of BMP signaling in primary cilia, enabling us to unravel the potential pathogenesis of skeletal ciliopathies.