The inositol phosphatase SHIP1 regulates skeletal development

Safari, Fatemeh; Yeoh, Jeremy; Bringardner, Margaux; Siegrist, Mark; Dolder, Silvia; Strunz, Franziska; Hofstetter, Willy; Krebs, Philippe (April 2021). The inositol phosphatase SHIP1 regulates skeletal development. Bone reports, 14, p. 100795. Elsevier 10.1016/j.bonr.2021.100795

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Background/Introduction: Src-homology (SH) 2 domain-containing inositol-5-phosphatase 1 (SHIP1) is a lipid phosphatase expressed mainly in hematopoietic cells. SHIP1 regulates cell proliferation, differentiation, and survival via the PI3K/Akt signaling pathway. SHIP1-deficient (Styx) mice are osteoporotic, which is associated with an increased number of osteoclasts (OC).

Purpose: This study aimed to investigate the underlying mechanisms through which SHIP1 controls osteoporosis.

Methods: Osteoclast progenitor cells (OPC) were generated by incubating bone marrow cells with CSF-1. To develop OC, OPC from Styx, Styx het (heterozygous) and wt (wild type) mice were cultured with RANKL and CSF-1. Osteoclastogenesis was evaluated using an XTT cell viability assay, TRAP activity (OC marker) and qRT-PCR. Micro-computed tomography (Micro-CT) of vertebrae and femora were performed to evaluate the bone structure.

Results: Deficiency in SHIP1 affected several aspects of bone. Compared to Styx het and wt controls, OPC-derived Styx OC presented several developmental defects, including a lower TRAP/XTT ratio and a 52% decrease in Calcr transcripts (encoding for the Calcitonin Receptor) (p<0.001). In vivo, there was a strong reduction of BV/TV in vertebrae and femora of Styx versus wt animals (39.6% and 35%, respectively, p<0.01). In particular, trabeculae in Styx vertebrae were increased by 8% (p<0.05) in numbers while decreased by 37% in thickness (p<0.001). In contrast, in Styx femora both the number and thickness of the trabeculae were decreased by 16% and 14%, respectively. These different phenotypes in Styx femora versus vertebrae indicate different paths to osteoporosis in bones with primary or secondary spongiosa.

Conclusion(s): Taken together, our data indicate a central role for SHIP1-dependent PI3K/Akt signalling in bone remodeling. Further investigation will address the role of osteoblasts in the development of osteoporosis in SHIP1-deficient Styx mice.

Item Type:

Conference or Workshop Item (Abstract)


04 Faculty of Medicine > Service Sector > Institute of Pathology > Immunopathology
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR)
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Knochenbiologie & Orthopädische Forschung
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Knochenbiologie & Orthopädische Forschung

Graduate School:

Graduate School for Cellular and Biomedical Sciences (GCB)

UniBE Contributor:

Safari, Fatemeh, Siegrist, Mark, Dolder, Silvia, Strunz, Franziska Silvia, Hofstetter, Wilhelm (B), Krebs, Philippe


600 Technology > 610 Medicine & health








Fatemeh Safari

Date Deposited:

23 Nov 2022 14:34

Last Modified:

02 Mar 2023 23:36

Publisher DOI:





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