Yubei Chen1, Qiqi Fan1, Han Zhang1, Dike Tao1, Yibin Wang2, Rui Yue2, Yao Sun1. 1. Department of Implantology, School & Hospital of Stomatology, Tongji University, Shanghai Engineering Research Center of Tooth Restoration and Regeneration, Shanghai, China. 2. Institute for Regenerative Medicine, Shanghai East Hospital, Shanghai Key Laboratory of Signaling and Disease Research, School of Life Sciences and Technology, Tongji University, Shanghai, China.
Abstract
BACKGROUND: Primary cilia influence cell function and tissue development. Ciliary signaling is mediated by two intraflagellar transport (IFT) protein complexes, IFT-A and IFT-B. The IFT-A complex is responsible for retrograde transport, and IFT140 is a core protein in the A complex. Mutations in IFT140 cause a variety of skeletal disorders. However, the expression and role of IFT140 during bone development remain unclear. In this study, to further explore the potential role of IFT140 in osteogenesis, we used cell lineage tracing and conditional knockout to analyze the distribution and function of IFT140-positive cells during bone formation. RESULTS: In newborn Ift140-creER; R26RtdTomato mice, IFT140-positive cells were mainly located in the medullary cavity and then migrated to and differentiated on the surface of trabecular and cortical bone. In contrast, the number of IFT140-positive cells significantly decreased in the adult stage, and these cells were only located in the bone marrow cavity for a short time. In Osx-cre; Ift140flox/flox mice, the loss of IFT140 in preosteoblasts caused bone loss in the trabecular bone area at 10 weeks. CONCLUSION: The results revealed that IFT140-positive cells mainly contribute to the early stage of bone formation.
BACKGROUND: Primary cilia influence cell function and tissue development. Ciliary signaling is mediated by two intraflagellar transport (IFT) protein complexes, IFT-A and IFT-B. The IFT-A complex is responsible for retrograde transport, and IFT140 is a core protein in the A complex. Mutations in IFT140 cause a variety of skeletal disorders. However, the expression and role of IFT140 during bone development remain unclear. In this study, to further explore the potential role of IFT140 in osteogenesis, we used cell lineage tracing and conditional knockout to analyze the distribution and function of IFT140-positive cells during bone formation. RESULTS: In newborn Ift140-creER; R26RtdTomato mice, IFT140-positive cells were mainly located in the medullary cavity and then migrated to and differentiated on the surface of trabecular and cortical bone. In contrast, the number of IFT140-positive cells significantly decreased in the adult stage, and these cells were only located in the bone marrow cavity for a short time. In Osx-cre; Ift140flox/flox mice, the loss of IFT140 in preosteoblasts caused bone loss in the trabecular bone area at 10 weeks. CONCLUSION: The results revealed that IFT140-positive cells mainly contribute to the early stage of bone formation.