Arl13b promotes the proliferation, migration, osteogenesis, and mechanosensation of osteoblasts

Abstract

Primary cilia are microtubule-based organelles presenting on the surface of most postmitotic mammalian cells. As being signaling hubs and sensory organelles, primary cilia can respond to mechanical and chemical stimuli from the extracellular environment. Arl13b (ADP-ribosylation factor-like 13B), an atypical Arf/Arl family GTPase, was identified in genetic screening as a protein essential for maintaining the integrity of cilia and neural tubes. Previous studies on Arl13b have mostly focused on its role in the development of neural tubes, polycystic kidneys, and tumors, but no role in bone patterns was described. This study reported the essential roles of Arl13b in bone formation and osteogenic differentiation. Arl13b was highly expressed in bone tissues and osteoblasts, positively correlated with osteogenic activity during bone development. Furthermore, Arl13b was essential for primary cilium maintenance and Hedgehog signaling activation in osteoblasts. Arl13b knockdown in osteoblasts decreased the length of primary cilia and the upregulated levels of Gli1, Smo, and Ptch1 upon Smo agonist treatment. Additionally, Arl13b knockdown inhibited cell proliferation and migration. Moreover, Arl13b mediated osteogenesis and cell mechanosensation. Cyclic tension strain upregulated the Arl13b expression. Arl13b knockdown suppressed osteogenesis and mitigated cyclic tension strain-induced osteogenesis. These results suggest that Arl13b have important roles in bone formation and mechanosensation.

Keywords: Arl13b; Hedgehog signaling; Mechanosensation; Osteoblast; Osteogenesis; Primary cilium.