Primary cilia in growth plates orchestrate long bone development.

The growth plate plays a crucial role in long bone development and elongation, housing stem cells that contribute to bone formation. This study investigates the role of primary cilia, specialized organelles that regulate stem cell fate, in the development and repair of long bones. Here, we report the presence of primary cilia in all zones of the growth plate, particularly during embryonic development. Spatial transcriptomics and analysis of conditional knockout (CKO) mice identified that primary cilia mediate critical developmental signaling pathways within the growth plate. Disruption of primary cilia in growth plate chondroblasts or osteoblasts impaired long bone development by activating the Wnt signaling pathway and disrupting the cellular stemness. This resulted in elevated Mmp13 secretion, abnormal mineralization, and structural defects, ultimately hindering bone elongation. Time-lapse imaging showed an increased frequency of abnormal mitosis and a reduced rate of asymmetric division in skeletal stem cells (SSCs) from CKO mice. In conclusion, our findings indicated that primary cilia are critical for long bone development, regulating stem cell fate through key signaling pathways. Loss of primary cilia leads to excessive Wnt signaling and disruption of SSC stemness, impairing bone elongation. This study highlights the essential role of primary cilia in bone development and suggests potential therapeutic targets for skeletal disorders.