Schlafen2 mutation in mice causes an osteopetrotic phenotype due to a decrease in the number of osteoclast progenitors.

Sci Rep 2018 08 29;8(1):13005. Epub 2018 Aug 29.

Department of Physiology and Cell Biology, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel.

Osteoclasts are the bone resorbing cells that derive from myeloid progenitor cells. Although there have been recent advancements in the ability to identify osteoclast progenitors, very little is known about the molecular mechanisms governing their homeostasis. Here, by analyzing the normalized phylogenetic profiles of the Schlafen (Slfn) gene family, we found that it co-evolved with osteoclast-related genes. Following these findings, we used a Slfn2 loss-of-function mutant mouse, elektra, to study the direct role of Slfn2 in osteoclast development and function. Slfn2 mice exhibited a profound increase in their cancellous bone mass and a significant reduction in osteoclast numbers. In addition, monocyte cultures from the bone marrow of Slfn2 mice showed a reduction in osteoclast number and total resorption area. Finally, we show that the bone marrow of Slfn2 mice have significantly less CD11bLy6C osteoclast precursors. Overall, our data suggest that Slfn2 is required for normal osteoclast differentiation and that loss of its function in mice results in an osteopetrotic phenotype.

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http://dx.doi.org/10.1038/s41598-018-31428-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6115409PMC
August 2018
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