Primary cilia and PTH1R interplay in the regulation of osteogenic actions

Abstract

Primary cilia are subcellular structures specialized in sensing different stimuli in a diversity of cell types. In bone, the primary cilium is involved in mechanical sensing and transduction of signals that regulate the behavior of mesenchymal osteoprogenitors, osteoblasts and osteocytes. To perform its functions, the primary cilium modulates a plethora of molecules including those stimulated by the parathyroid hormone (PTH) receptor type I (PTH1R), a master regulator of osteogenesis. Binding of the agonists PTH or PTH-related protein (PTHrP) to the PTH1R or direct agonist-independent stimulation of the receptor activate PTH1R signaling pathways. In turn, activation of PTH1R leads to regulation of bone formation and remodeling. Herein, we describe the structure, function and molecular partners of primary cilia in the context of bone, playing special attention to those signaling pathways that are mediated directly or indirectly by PTH1R in association with primary cilia during the process of osteogenesis.

Keywords: Bone; Ossification; Osteogenesis; PTH receptor type I; PTH-related protein; Parathyroid hormone; Primary cilium; Signaling pathways.