Csf1-KO Mouse

Csf1, also known as macrophage colony-stimulating factor 1, is the primary growth factor essential for the control of monocyte and macrophage differentiation, survival, proliferation and renewal [4]. It is a key regulator in pathways related to immune cell function, tissue repair, and bone remodeling. Csf1 binds to its receptor Csf1R, activating downstream signaling cascades that are crucial for the normal development and function of macrophages and related cell populations [1,2,4,5,6,7].

In a Csf1 conditional knockout (CKO) mouse model using AdipoqCre to deplete Csf1 in marrow adipogenic lineage precursors (MALPs), the mice had increased femoral trabecular bone mass due to diminished osteoclasts in the femoral secondary spongiosa region. These mice were also resistant to LPS-induced calvarial osteolysis, and had reduced bone marrow cellularity, hematopoietic progenitors, and macrophages. This indicates that MALPs-derived Csf1 is required for osteoclast formation and hematopoiesis in bone [3].

In conclusion, Csf1 plays essential roles in the development and maintenance of monocyte-macrophage lineages, bone remodeling, and hematopoiesis. The Csf1 CKO mouse model has provided insights into its role in bone-related diseases, highlighting its potential as a therapeutic target for conditions involving abnormal bone metabolism and immune-related disorders [3].

References:

1. Fujiwara, Tomohiro, Yakoub, Mohamed A, Chandler, Andrew, Purdue, Ed, Healey, John H. 2021. CSF1/CSF1R Signaling Inhibitor Pexidartinib (PLX3397) Reprograms Tumor-Associated Macrophages and Stimulates T-cell Infiltration in the Sarcoma Microenvironment. In Molecular cancer therapeutics, 20, 1388-1399. doi:10.1158/1535-7163.MCT-20-0591. https://pubmed.ncbi.nlm.nih.gov/34088832/

2. Huang, Yao-Hui, Cai, Kun, Xu, Peng-Peng, Ji, Meng-Meng, Zhao, Wei-Li. 2021. CREBBP/EP300 mutations promoted tumor progression in diffuse large B-cell lymphoma through altering tumor-associated macrophage polarization via FBXW7-NOTCH-CCL2/CSF1 axis. In Signal transduction and targeted therapy, 6, 10. doi:10.1038/s41392-020-00437-8. https://pubmed.ncbi.nlm.nih.gov/33431788/

3. Zhong, Leilei, Lu, Jiawei, Fang, Jiankang, Dyment, Nathanial, Qin, Ling. 2023. Csf1 from marrow adipogenic precursors is required for osteoclast formation and hematopoiesis in bone. In eLife, 12, . doi:10.7554/eLife.82112. https://pubmed.ncbi.nlm.nih.gov/36779854/

4. Sehgal, Anuj, Irvine, Katharine M, Hume, David A. 2021. Functions of macrophage colony-stimulating factor (CSF1) in development, homeostasis, and tissue repair. In Seminars in immunology, 54, 101509. doi:10.1016/j.smim.2021.101509. https://pubmed.ncbi.nlm.nih.gov/34742624/

5. Wang, Qian, Wang, Jianhong, Xu, Ke, Luo, Zhibin. 2024. Targeting the CSF1/CSF1R signaling pathway: an innovative strategy for ultrasound combined with macrophage exhaustion in pancreatic cancer therapy. In Frontiers in immunology, 15, 1481247. doi:10.3389/fimmu.2024.1481247. https://pubmed.ncbi.nlm.nih.gov/39416792/

6. Zhou, Yamei, Zeng, Jia, Tu, Yuanyuan, Zhu, Manhui, Liu, Xiaojuan. . CSF1/CSF1R-mediated Crosstalk Between Choroidal Vascular Endothelial Cells and Macrophages Promotes Choroidal Neovascularization. In Investigative ophthalmology & visual science, 62, 37. doi:10.1167/iovs.62.3.37. https://pubmed.ncbi.nlm.nih.gov/33764399/

7. Assi, Tarek, Moussa, Tania, Ngo, Carine, Vibert, Julien, Cesne, Axel Le. 2025. Therapeutic advances in Tenosynovial giant cell Tumor: Targeting the CSF1/CSF1R axis. In Cancer treatment reviews, 134, 102904. doi:10.1016/j.ctrv.2025.102904. https://pubmed.ncbi.nlm.nih.gov/40020639/