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Blockade of the colony-stimulating factor-1 receptor reverses bone loss in osteoporosis mouse models

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Abstract

Background

Mice lacking either colony-stimulating factor-1 (CSF-1) or its receptor, CSF-1R, display osteopetrosis. Accordingly, genetic deletion or pharmacological blockade of CSF-1 prevents the bone loss associated with estrogen deficiency. However, the role of CSF-1R in osteoporosis models of type-1 diabetes (T1D) and ovariectomy (OVX) has not been examined. Thus, we evaluated whether CSF-1R blockade would relieve the bone loss in a model of primary osteoporosis (female mice with OVX) and a model of secondary osteoporosis (female with T1D) using micro-computed tomography.

Methods

Female ICR mice at 10 weeks underwent OVX or received five daily administrations of streptozotocin (ip, 50 mg/kg) to induce T1D. Four weeks after OVX and 14 weeks after first injection of streptozotocin, mice received an anti-CSF-1R (2G2) antibody (10 mg/kg, ip; once/week for 6 weeks) or vehicle. At the last day of antibody administration, mice were sacrificed and femur and tibia were harvested for micro-computed tomography analysis.

Results

Mice with OVX had a significant loss of trabecular bone at the distal femoral and proximal tibial metaphysis. Chronic treatment with anti-CSF-1R significantly reversed the trabecular bone loss at these anatomical sites. Streptozotocin-induced T1D resulted in significant loss of trabecular bone at the femoral neck and cortical bone at the femoral mid-diaphysis. Chronic treatment with anti-CSF-1R antibody significantly reversed the bone loss observed in mice with T1D.

Conclusion

Our results demonstrate that blockade of CSF-1R signaling reverses bone loss in two different mouse models of osteoporosis.

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Acknowledgements

This work was supported by the Consejo Nacional de Ciencia y Tecnología (the Mexican Nacional Council for Science and Technology) [CB-2014 240829, PDCPN-2015-01-191, and Apoyo para Actividades Científicas, Tecnológicas y de Innovación 2019-299535]. We deeply acknowledge to Carola H. Ries for her helpful support to achieve the antibody donation.

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Authors and Affiliations

  1. Laboratorio de Farmacología, Unidad Académica Multidisciplinaria Reynosa-Aztlán, Universidad Autónoma de Tamaulipas, Calle 16 y Lago de Chapala, Col. Aztlán, 88740, Reynosa, TAMPS, México

    Arisaí Martínez-Martínez, Enriqueta Muñoz-Islas, Martha B. Ramírez-Rosas, Rosa I. Acosta-González, Héctor F. Torres-Rodríguez & Juan M. Jiménez-Andrade

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  1. Arisaí Martínez-Martínez
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Contributions

JMJA, EMI and MBRR conceived the project. AMM, EMI, HFTR and MBRR performed the experiments. JMJA, RIAG and MBRR analyzed and interpreted the data. JMJA, AMM, EMI, MBRR, RIAG and HFTR wrote and edited the manuscript. All authors have read and approved the manuscript. JMJA obtained grant funding.

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Correspondence to Juan M. Jiménez-Andrade.

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Martínez-Martínez, A., Muñoz-Islas, E., Ramírez-Rosas, M.B. et al. Blockade of the colony-stimulating factor-1 receptor reverses bone loss in osteoporosis mouse models. Pharmacol. Rep 72, 1614–1626 (2020). https://doi.org/10.1007/s43440-020-00091-5

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