We further show that SYK centrally mediates signaling upstream of caspase-1 and caspase-8 activation and principally up-regulates NF-κB and IL-1β signaling in <i>Pstpip2<sup>cmo</sup></i> mice and thereby induces <i>cmo.</i> These results provide a rationale for directly targeting SYK and its downstream signaling components in CRMO.
Recent work in the chronic multifocal osteomyelitis (cmo) mouse model demonstrates that the disease is IL-1-mediated, that neutrophils are critical effector cells and that both caspase-1 and caspase-8 play redundant roles in mediating the cleavage of pro-IL-1β into its biologically active form.
We further show that SYK centrally mediates signaling upstream of caspase-1 and caspase-8 activation and principally up-regulates NF-κB and IL-1β signaling in <i>Pstpip2<sup>cmo</sup></i> mice and thereby induces <i>cmo.</i> These results provide a rationale for directly targeting SYK and its downstream signaling components in CRMO.
Recent work in the chronic multifocal osteomyelitis (cmo) mouse model demonstrates that the disease is IL-1-mediated, that neutrophils are critical effector cells and that both caspase-1 and caspase-8 play redundant roles in mediating the cleavage of pro-IL-1β into its biologically active form.
Parallel developmental disorders in other species could provide complementary models for human rare diseases by uncovering new candidate genes, improving the understanding of the molecular mechanisms and opening possibilities for therapeutic trials.We performed various experiments, e.g. combined genome-wide association and next generation sequencing, to investigate the clinico-pathological features and genetic causes of three developmental syndromes in dogs, including craniomandibular osteopathy (CMO), a previously undescribed skeletal syndrome, and dental hypomineralization, for which we identified pathogenic variants in the canine SLC37A2 (truncating splicing enhancer variant), SCARF2 (truncating 2-bp deletion) and FAM20C (missense variant) genes, respectively.
Our data implicate FBLIM1 in the pathogenesis of sterile bone inflammation and our findings suggest CRMO is a disorder of chronic inflammation and imbalanced bone remodeling.
Filamin-binding LIM protein 1 (FBLIM1) is related to regulation of inflammatory responses, such as chronic recurrent multifocal osteomyelitis; however, the relevance of FBLIM1 in oral squamous cell carcinoma (OSCC) is unknown.
Thus, impaired ERK1/2 signaling with subsequently reduced Sp-1 expression and H3S10 phosphorylation of the IL10 promoter may centrally contribute to the pathophysiology of CRMO.
As <i>cmo</i> disease in mice, the experimental model analogous to human CRMO, is mediated specifically by interleukin (IL)-1β, and not by IL-1α, delineating the molecular pathways contributing to pathogenic IL-1β production is crucial to developing targeted therapies.
Recent work in the chronic multifocal osteomyelitis (cmo) mouse model demonstrates that the disease is IL-1-mediated, that neutrophils are critical effector cells and that both caspase-1 and caspase-8 play redundant roles in mediating the cleavage of pro-IL-1β into its biologically active form.
Recent work in the chronic multifocal osteomyelitis (cmo) mouse model demonstrates that the disease is IL-1-mediated, that neutrophils are critical effector cells and that both caspase-1 and caspase-8 play redundant roles in mediating the cleavage of pro-IL-1β into its biologically active form.
As <i>cmo</i> disease in mice, the experimental model analogous to human CRMO, is mediated specifically by interleukin (IL)-1β, and not by IL-1α, delineating the molecular pathways contributing to pathogenic IL-1β production is crucial to developing targeted therapies.