Septins are critical regulators of osteoclastic bone resorption

Scientific Reports
Anaïs M J MøllerKent Søe

Abstract

Septins are known to play key roles in supporting cytoskeletal stability, vesicular transport, endo-/exocytosis, stabilizing cellular membranes and forming diffusion barriers. Their function in mammalian cells is poorly investigated. The osteoclast offers an interesting tool to investigate septins because all cellular activities septins were reported to be involved in are critical for osteoclasts. However, the existence of septins in osteoclasts has not even been reported. Here we show that the SEPT9 gene and Septin 9 (SEPT9) protein are expressed and synthesized during differentiation of human osteoclasts. Pharmacological stabilization of septin filaments dose dependently inhibits bone resorption of human osteoclasts in vitro suggesting a role for septins in bone resorption. Attesting to this, conditional deletion of Sept9 in mice leads to elevated levels of trabecular bone and diminished femoral growth in vivo. Finally, systematic interrogation of the spatial organization of SEPT9 by confocal microscopy reveals that SEPT9 is closely associated to the structures known to be critical for osteoclast activity. We propose that septins in general and SEPT9 in particular play a previously unappreciated role in osteoclastic bone reso...Continue Reading

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Citations

Oct 12, 2020·The American Journal of Pathology·Andrei I IvanovFlorian Rieder
Apr 17, 2021·Frontiers in Cell and Developmental Biology·Jean-Marie DelaisseNiels Marcussen

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Methods Mentioned

BETA
confocal microscopy
PCR
Assay
light microscopy
Profiler
transgenic

Software Mentioned

Imaris
GraphPad Prism
STATA
GraphPad
ImageJ
Linescan Intensity Profiler ( MATLAB

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