Dysregulation of macrophage colony stimulating factor in Paget’s disease of bone

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ID: 333236
2026
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Abstract
Abstract Objective To determine if common genetic variants at the chromosome 1p13 locus which predisposes to Paget’s Disease of Bone (PDB) regulate Macrophage Colony stimulating factor (M-CSF) expression in bone cells and to determine if there is dysregulation of M-CSF in patients with PDB. Methods The regions surrounding single nucleotide polymorphisms (SNP) previously associated with PDB at a genome wide significant level were deleted in clones of MG63 osteoblast-like cells using CRISPR/Cas and levels of M-CSF mRNA and protein were evaluated in cells with and without deletions. Serum M-CSF was measured by ELISA in PDB and controls and values in patients were related to clinical features of PDB and biochemical markers of bone remodelling. Results Deletion of the region surrounding rs484959 increased expression of M-CSF mRNA by 1.31 fold [95%,1.04-1.58], p = 0.026 and M-CSF protein by 1.91 fold [1.25-2.57], p = 0.013, compared with control cells. Serum M-CSF was significantly elevated in PDB versus controls (mean ± SD = 781.7 ± 678 vs. 541 ± 491 pg/mL, p < 0.001). Furthermore, M-CSF levels were associated with number of affected bones (p = 0.029), bodily pain assessed by SF-36 (p = 0.026) and biochemical markers of bone turnover. Conclusion The rs484959 SNP is a regulatory variant which modulates M-CSF mRNA and protein expression in osteoblasts. Serum M-CSF is increased in PDB, is associated with pain, disease extent and biochemical markers of bone remodelling. This suggest that there is dysregulation of M-CSF in PDB and that this cytokine may play a role in pathogenesis of the disease.
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Authors Asim Azfer, Kathryn M Berg, Katya Johnson, Pippa A. Thomson, James F. Wilson, Sachin Wani, Jonathan C. Y. Tang, Omar Albagha, Stuart H. Ralston
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Journal Lara D. Veeken
Year 2026
DOI
10.1093/rheumatology/keag571
URL
https://doi.org/10.1093/rheumatology/keag571
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