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

A, Martínez-Martínez; Muñoz-Islas, Enriqueta; Ramírez‐Rosas, Martha B.; Acosta-González, Rosa Issel; Torres-Rodríguez, Héctor Fabián; Jiménez-Andrade, Juan Miguel

doi:10.1007/s43440-020-00091-5

Cited by 5 publications

(3 citation statements)

References 48 publications

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“…Blocking antibodies are potentially more effective because they can saturate surface receptors and have more favorable half-life/pharmacokinetics. Both anti-CSF1R and anti-CSF1 antibodies have been found to ablate OCL and/or inhibit OCL activity with consequent reduction in bone loss in mice [50,71,[132][133][134]. The effects seem to be specific to excess OCL activity.…”

Section: Csf1r and Homeostasismentioning

confidence: 95%

CSF1R as a Therapeutic Target in Bone Diseases: Obvious but Not so Simple

Hume

Batoon

Sehgal

et al. 2022

Curr Osteoporos Rep

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Purpose of Review The purpose of the review is to summarize the expression and function of CSF1R and its ligands in bone homeostasis and constraints on therapeutic targeting of this axis. Recent Findings Bone development and homeostasis depends upon interactions between mesenchymal cells and cells of the mononuclear phagocyte lineage (MPS), macrophages, and osteoclasts (OCL). The homeostatic interaction is mediated in part by the systemic and local production of growth factors, macrophage colony-stimulating factor (CSF1), and interleukin 34 (IL34) that interact with a receptor (CSF1R) expressed exclusively by MPS cells and their progenitors. Loss-of-function mutations in CSF1 or CSF1R lead to loss of OCL and macrophages and dysregulation of postnatal bone development. MPS cells continuously degrade CSF1R ligands via receptor-mediated endocytosis. As a consequence, any local or systemic increase or decrease in macrophage or OCL abundance is rapidly reversible. Summary In principle, both CSF1R agonists and antagonists have potential in bone regenerative medicine but their evaluation in disease models and therapeutic application needs to carefully consider the intrinsic feedback control of MPS biology.

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Section: Csf1r and Homeostasismentioning

confidence: 95%

CSF1R as a Therapeutic Target in Bone Diseases: Obvious but Not so Simple

Hume

Batoon

Sehgal

et al. 2022

Curr Osteoporos Rep

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“…It promotes the release of proinflammatory chemokines to IL-34 and colony stimulating factor 1 (CSF1) and thus plays an important role in innate immunity and inflammation. CSF1 plays an important role in the regulation of osteoclast proliferation and differentiation and bone resorption, and it is necessary for normal bone and tooth development [ 39 – 41 ]. Studies have shown that CSF1R is a DEG between those with a torn meniscus in the knee joint and those with end-stage knee OA [ 42 ].…”

Section: Discussionmentioning

confidence: 99%

Identification and development of a novel 5-gene diagnostic model based on immune infiltration analysis of osteoarthritis

Han

Gong

et al. 2021

J Transl Med

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Background Osteoarthritis (OA), which is due to the progressive loss and degeneration of articular cartilage, is the leading cause of disability worldwide. Therefore, it is of great significance to explore OA biomarkers for the prevention, diagnosis, and treatment of OA. Methods and materials The GSE129147, GSE57218, GSE51588, GSE117999, and GSE98918 datasets with normal and OA samples were downloaded from the Gene Expression Omnibus (GEO) database. The GSE117999 and GSE98918 datasets were integrated, and immune infiltration was evaluated. The differentially expressed genes (DEGs) were analyzed using the limma package in R, and weighted gene co-expression network analysis (WGCNA) was used to explore the co-expression genes and co-expression modules. The co-expression module genes were analyzed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. A protein–protein interaction (PPI) network was constructed using the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) database, and hub genes were identified by the degree, MNC, closeness, and MCC algorithms. The hub genes were used to construct a diagnostic model based on support vector machines. Results The Immune Score in the OA samples was significantly higher than in the normal samples, and a total of 2313 DEGs were identified. Through WGCNA, we found that the yellow module was significantly positively correlated with the OA samples and Immune Score and negatively correlated with the normal samples. The 142 DEGs of the yellow module were related to biological processes such as regulation of inflammatory response, positive regulation of inflammatory response, blood vessel morphogenesis, endothelial cell migration, and humoral immune response. The intersections of the genes obtained by the 4 algorithms resulted in 5 final hub genes, and the diagnostic model constructed with these 5 genes showed good performance in the training and validation cohorts. Conclusions The 5-gene diagnostic model can be used to diagnose OA and guide clinical decision-making.

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“…Anti-M-CSF antibodies prevent osteoclast formation and bone resorption in OVX mice [ 35 ], which suggests that M-CSF is a therapeutic target of bone loss in OVX mice. Recently, it has also been reported that anti-CSF-1R antibodies (2G2) inhibited bone loss in an osteoporosis mouse model [ 36 ]. Here, we used a different M-CSF blocking antibody, an anti-c-fms antibody (AFS98) and we obtained similar results for the inhibition of osteoporosis.…”

Section: Discussionmentioning

confidence: 99%

Anti-c-fms Antibody Prevents Osteoclast Formation and Bone Resorption in Co-Culture of Osteoblasts and Osteoclast Precursors In Vitro and in Ovariectomized Mice

Nara

Kitaura

Ogawa

et al. 2020

IJMS

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Osteoporosis morphology is characterized by bone resorption and decreases in micro-architecture parameters. Anti-osteoporosis therapy targets osteoclasts because bone resorption is a unique function of osteoclasts. Anti-c-fms antibodies against the receptor for macrophage colony-stimulating factor (M-CSF) inhibit osteoclast formation and bone resorption in vitro and in vivo. However, the effect of anti-c-fms antibodies on bone resorption in ovariectomized (OVX) mice is unknown. In this study, we evaluated the effect of anti-c-fms antibodies on osteoclast formation and bone resorption in osteoblast–osteoclast precursor co-culture in vitro and in OVX mice. Osteoblast and osteoclast precursor co-cultures treated with anti-c-fms antibodies showed significantly inhibited osteoclast formation, while cultures without anti-c-fms antibody treatment showed osteoclast formation. However, anti-c-fms antibodies did not change the receptor activator of nuclear factor kappa-B ligand (RANKL) or osteoprotegrin (OPG) expression during osteoblast and osteoclast differentiation in vitro. These results indicate that anti-c-fms antibodies directly affected osteoclast formation from osteoclast precursors in co-culture. OVX mice were treated with intraperitoneal injections of anti-c-fms antibody. The trabecular bone structure of the femur was assessed by micro-computer tomography. The anti-c-fms antibody inhibited osteoclast formation and bone loss compared with PBS-treated OVX mice. These results indicate potential for the therapeutic application of anti-c-fms antibodies for postmenopausal osteoporosis.

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

Cited by 5 publications

References 48 publications

CSF1R as a Therapeutic Target in Bone Diseases: Obvious but Not so Simple

CSF1R as a Therapeutic Target in Bone Diseases: Obvious but Not so Simple

Identification and development of a novel 5-gene diagnostic model based on immune infiltration analysis of osteoarthritis

Anti-c-fms Antibody Prevents Osteoclast Formation and Bone Resorption in Co-Culture of Osteoblasts and Osteoclast Precursors In Vitro and in Ovariectomized Mice

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