Osteoclasts are not a source of SLIT3.

Bone Research
Na LiMatthew B Greenblatt

Abstract

The axon guidance cue SLIT3 was identified as an osteoanabolic agent in two recent reports. However, these reports conflict in their nomination of osteoblasts versus osteoclasts as the key producers of skeletal SLIT3 and additionally offer conflicting data on the effects of SLIT3 on osteoclastogenesis. Here, aiming to address this discrepancy, we found no observable SLIT3 expression during human or mouse osteoclastogenesis and the only modest SLIT3-mediated effects on osteoclast differentiation. Conditional deletion of SLIT3 in cathepsin K (CTSK)-positive cells, including osteoclasts, had no effect on the number of osteoclast progenitors, in vitro osteoclast differentiation, overall bone mass, or bone resorption/formation parameters. Similar results were observed with the deletion of SLIT3 in LysM-positive cells, including osteoclast lineage cells. Consistent with this finding, bone marrow chimeras made from Slit3 -/- donors that lacked SLIT3 expression at all stages of osteoclast development displayed normal bone mass relative to controls. Taken in context, multiple lines of evidence were unable to identify the physiologic function of osteoclast-derived SLIT3, indicating that osteoblasts are the major source of skeletal SLIT3.

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Citations

Aug 9, 2020·Gynecological Endocrinology : the Official Journal of the International Society of Gynecological Endocrinology·Alberto Hidalgo-BravoRafael Velázquez-Cruz

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Methods Mentioned

BETA
PCR
RNA-seq
flow cytometry
fluorescence-activated cell sorting
Assay
X-ray
FACS

Software Mentioned

FlowJo
GraphPad
STAR
R package
SAMtools
Osteomeasure Analysis System
DESeq2
GraphPad Prism
Image J

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