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ELMO1 signaling is a promoter of osteoclast function and bone loss

Sanja Arandjelovic, Justin S. A. Perry, Ming Zhou, Adam Ceroi (UGent) , Igor Smirnov, Scott F. Walk, Laura S. Shankman, Isabelle Cambré (UGent) , Suna Onengut-Gumuscu, Dirk Elewaut (UGent) , et al.
(2021) NATURE COMMUNICATIONS. 12(1).
Author
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Abstract
Osteoporosis affects millions worldwide and is often caused by osteoclast induced bone loss. Here, we identify the cytoplasmic protein ELMO1 as an important 'signaling node' in osteoclasts. We note that ELMO1 SNPs associate with bone abnormalities in humans, and that ELMO1 deletion in mice reduces bone loss in four in vivo models: osteoprotegerin deficiency, ovariectomy, and two types of inflammatory arthritis. Our transcriptomic analyses coupled with CRISPR/Cas9 genetic deletion identify Elmo1 associated regulators of osteoclast function, including cathepsin G and myeloperoxidase. Further, we define the 'ELMO1 interactome' in osteoclasts via proteomics and reveal proteins required for bone degradation. ELMO1 also contributes to osteoclast sealing zone on bone-like surfaces and distribution of osteoclast-specific proteases. Finally, a 3D structure-based ELMO1 inhibitory peptide reduces bone resorption in wild type osteoclasts. Collectively, we identify ELMO1 as a signaling hub that regulates osteoclast function and bone loss, with relevance to osteoporosis and arthritis. Osteoporosis and bone fractures affect millions of patients worldwide and are often due to increased bone resorption. Here the authors identify the cytoplasmic protein ELMO1 as an important 'signaling node' promoting the bone resorption function of osteoclasts.
Keywords
ONE-STEP ELISA, DEGRADATION-PRODUCTS, NUCLEOTIDE EXCHANGE, DISEASE, DATABASE, INHIBITORS, DOCK180, PROTEIN, MOUSE, CELLS

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MLA
Arandjelovic, Sanja, et al. “ELMO1 Signaling Is a Promoter of Osteoclast Function and Bone Loss.” NATURE COMMUNICATIONS, vol. 12, no. 1, 2021, doi:10.1038/s41467-021-25239-6.
APA
Arandjelovic, S., Perry, J. S. A., Zhou, M., Ceroi, A., Smirnov, I., Walk, S. F., … Ravichandran, K. (2021). ELMO1 signaling is a promoter of osteoclast function and bone loss. NATURE COMMUNICATIONS, 12(1). https://doi.org/10.1038/s41467-021-25239-6
Chicago author-date
Arandjelovic, Sanja, Justin S. A. Perry, Ming Zhou, Adam Ceroi, Igor Smirnov, Scott F. Walk, Laura S. Shankman, et al. 2021. “ELMO1 Signaling Is a Promoter of Osteoclast Function and Bone Loss.” NATURE COMMUNICATIONS 12 (1). https://doi.org/10.1038/s41467-021-25239-6.
Chicago author-date (all authors)
Arandjelovic, Sanja, Justin S. A. Perry, Ming Zhou, Adam Ceroi, Igor Smirnov, Scott F. Walk, Laura S. Shankman, Isabelle Cambré, Suna Onengut-Gumuscu, Dirk Elewaut, Thomas P. Conrads, and Kodi Ravichandran. 2021. “ELMO1 Signaling Is a Promoter of Osteoclast Function and Bone Loss.” NATURE COMMUNICATIONS 12 (1). doi:10.1038/s41467-021-25239-6.
Vancouver
1.
Arandjelovic S, Perry JSA, Zhou M, Ceroi A, Smirnov I, Walk SF, et al. ELMO1 signaling is a promoter of osteoclast function and bone loss. NATURE COMMUNICATIONS. 2021;12(1).
IEEE
[1]
S. Arandjelovic et al., “ELMO1 signaling is a promoter of osteoclast function and bone loss,” NATURE COMMUNICATIONS, vol. 12, no. 1, 2021.
@article{8721317,
  abstract     = {{Osteoporosis affects millions worldwide and is often caused by osteoclast induced bone loss. Here, we identify the cytoplasmic protein ELMO1 as an important 'signaling node' in osteoclasts. We note that ELMO1 SNPs associate with bone abnormalities in humans, and that ELMO1 deletion in mice reduces bone loss in four in vivo models: osteoprotegerin deficiency, ovariectomy, and two types of inflammatory arthritis. Our transcriptomic analyses coupled with CRISPR/Cas9 genetic deletion identify Elmo1 associated regulators of osteoclast function, including cathepsin G and myeloperoxidase. Further, we define the 'ELMO1 interactome' in osteoclasts via proteomics and reveal proteins required for bone degradation. ELMO1 also contributes to osteoclast sealing zone on bone-like surfaces and distribution of osteoclast-specific proteases. Finally, a 3D structure-based ELMO1 inhibitory peptide reduces bone resorption in wild type osteoclasts. Collectively, we identify ELMO1 as a signaling hub that regulates osteoclast function and bone loss, with relevance to osteoporosis and arthritis. Osteoporosis and bone fractures affect millions of patients worldwide and are often due to increased bone resorption. Here the authors identify the cytoplasmic protein ELMO1 as an important 'signaling node' promoting the bone resorption function of osteoclasts.}},
  articleno    = {{4974}},
  author       = {{Arandjelovic, Sanja and Perry, Justin S. A. and Zhou, Ming and Ceroi, Adam and Smirnov, Igor and Walk, Scott F. and Shankman, Laura S. and Cambré, Isabelle and Onengut-Gumuscu, Suna and Elewaut, Dirk and Conrads, Thomas P. and Ravichandran, Kodi}},
  issn         = {{2041-1723}},
  journal      = {{NATURE COMMUNICATIONS}},
  keywords     = {{ONE-STEP ELISA,DEGRADATION-PRODUCTS,NUCLEOTIDE EXCHANGE,DISEASE,DATABASE,INHIBITORS,DOCK180,PROTEIN,MOUSE,CELLS}},
  language     = {{eng}},
  number       = {{1}},
  pages        = {{12}},
  title        = {{ELMO1 signaling is a promoter of osteoclast function and bone loss}},
  url          = {{http://doi.org/10.1038/s41467-021-25239-6}},
  volume       = {{12}},
  year         = {{2021}},
}
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