The Cytoplasmic Dynein Associated Protein NDE1 Regulates Osteoclastogenesis by Modulating M-CSF and RANKL Signaling Pathways

• Published in: Cells (Basel, Switzerland) Switzerland), 2021-12, Vol.11 (1), p.13
• Main Authors: Das, Bhaba K, Gogoi, Jyoti, Kannan, Aarthi, Gao, Ling, Xing, Weirong, Mohan, Subburaman, Zhao, Haibo
• Format: Article
• Language: English
• Subjects: Actin Cytoskeleton - metabolism; Animals; Antibodies; Bone and Bones - pathology; Bone marrow; Bone Marrow - pathology; Bone mass; bone remodeling; Bone resorption; Bone Resorption - pathology; Bone turnover; Cancellous bone; Cell Differentiation; Cell Proliferation; Cell Survival; Cloning; Cortical bone; cytoplasmic dynein; Cytoplasmic Dyneins - metabolism; Cytoskeleton; Dynein; Evolutionary conservation; Homeostasis; Kinases; Laboratories; Lysosomes; Macrophage colony-stimulating factor; Macrophage Colony-Stimulating Factor - metabolism; Mice; Mice, Inbred C57BL; Mice, Knockout; Microtubule-Associated Proteins - metabolism; Microtubules; Microtubules - metabolism; Monocytes - metabolism; Mutation; NDE1; NDEL1; Organelles; osteoclast; Osteoclastogenesis; Osteoclasts; Osteoclasts - metabolism; Osteoclasts - pathology; Osteogenesis; Osteoprogenitor cells; Potassium; Proteins; RANK Ligand - metabolism; Signal Transduction; TRANCE protein
• ISSN: 2073-4409; 2073-4409
• DOI: 10.3390/cells11010013

Cytoskeleton organization and lysosome secretion play an essential role in osteoclastogenesis and bone resorption. The cytoplasmic dynein is a molecular motor complex that regulates microtubule dynamics and transportation of cargos/organelles, including lysosomes along the microtubules. LIS1, NDE1, and NDEL1 belong to an evolutionary conserved pathway that regulates dynein functions. Disruption of the cytoplasmic dynein complex and deletion of LIS1 in osteoclast precursors arrest osteoclastogenesis. Nonetheless, the role of NDE1 and NDEL1 in osteoclast biology remains elusive. In this study, we found that knocking-down Nde1 expression by lentiviral transduction of specific shRNAs markedly inhibited osteoclastogenesis by attenuating the proliferation, survival, and differentiation of osteoclast precursor cells suppression of signaling pathways downstream of M-CSF and RANKL as well as osteoclast differentiation transcription factor NFATc1. To dissect how NDEL1 regulates osteoclasts and bone homeostasis, we generated conditional knockout mice in myeloid osteoclast precursors ( ) by crossing floxed mice with -Cre mice on C57BL/6J background. The mice developed normally. The µCT analysis of distal femurs and osteoclast differentiation and functional assays in cultures unveiled the similar bone mass in both trabecular and cortical bone compartments as well as intact osteoclastogenesis, cytoskeleton organization, and bone resorption in mice and cultures. Therefore, our results reveal a novel role of NDE1 in regulation of osteoclastogenesis and demonstrate that NDEL1 is dispensable for osteoclast differentiation and function.