ELMO1 signaling is a promoter of osteoclast function and bone loss

Sanja Arandjelovic*, 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, Kodi S. Ravichandran*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

17 Scopus citations


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.

Original languageEnglish
Article number4974
JournalNature Communications
Issue number1
StatePublished - 1 Dec 2021
Externally publishedYes


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