Biochemical Pharmacology, Journal Year: 2022, Volume and Issue: 207, P. 115377 - 115377
Published: Dec. 10, 2022
Language: Английский
Research, Journal Year: 2024, Volume and Issue: 7
Published: Jan. 1, 2024
Metal wear particles generated by the movement of joint prostheses inevitably lead to aseptic osteolytic damage and ultimately prosthesis loosening, which are aggravated various types regulated cell death bone. Nevertheless, exact cellular nature regulatory network underlying osteoferroptosis poorly understood. Here, we report that titanium (TP) induced severe peri-implant osteolysis ferroptotic changes with concomitant transcriptional repression a key anti-ferroptosis factor, GPX4, in mouse model calvarial osteolysis. GPX4 was accompanied an increase DNA methyltransferases (DNMTs) 1/3a/3b hypermethylation Gpx4 promoter, were partly mediated regulator/co-repressor KLF5 NCoR. Conversely, treatment SGI-1027, DNMT-specific inhibitor, resulted marked reversal promoter repression, as well improvement similar extent ferroptosis liproxstatin-1. This suggests epigenetic caused DNMT1/3a/3b have causal influence on TP-induced In cultured primary osteoblasts osteoclasts, observed primarily alleviated SGI-1027 inactivation-sensitive manner. Furthermore, developed strain haplodeficiency (Gpx4 Ob+/-) exhibited worsened control TP-treated calvaria largely abolished osteoprotective effects SGI-1027. Taken together, our results demonstrate elevation, resulting osteoblastic form critical pathway significantly contributes osteolysis, targeting DNMT aberration associated could be potential strategy prevent or slow down prosthesis-related complications.
Language: Английский
Citations
3
MedComm, Journal Year: 2024, Volume and Issue: 5(9)
Published: Sept. 1, 2024
Abstract Krüppel‐like factors (KLFs) are a family of basic transcription with three conserved Cys2/His2 zinc finger domains located in their C‐terminal regions. It is acknowledged that KLFs exert complicated effects on cell proliferation, differentiation, survival, and responses to stimuli. Dysregulation associated range diseases including cardiovascular disorders, metabolic diseases, autoimmune conditions, cancer, neurodegenerative diseases. Their multidimensional roles modulating critical pathways underscore the significance both physiological pathological contexts. Recent research also emphasizes crucial involvement complex interplay skeletal system. Despite substantial progress understanding various cellular processes, several gaps remain. Here, we elucidated multifaceted capabilities body health via compliable signaling pathways. The associations between energy metabolism epigenetic modification during bone reconstruction have been summarized. This review helps us better understand coupling pivotal functions multiple systems detailed mechanisms remodeling develop potential therapeutic strategies for clinical treatment by targeting KLF family.
Language: Английский
Citations
3
Bone Research, Journal Year: 2024, Volume and Issue: 12(1)
Published: Dec. 1, 2024
Abstract Osteoporosis (OP) is a common and fracture-prone skeletal disease characterized by deteriorated trabecular microstructure pathologically involving various forms of regulated bone cell death. However, the exact role, cellular nature regulatory mechanisms ferroptosis in OP are not fully understood. Here, we reported that femurs from ovariectomized (Ovx) mice exhibited pronounced iron deposition, ferroptosis, transcriptional suppression key anti-ferroptotic factor GPX4 (glutathione peroxidase 4). was accompanied hypermethylation Gpx4 promoter an increase DNA methyltransferases DNMT1/3a/3b transcriptionally promoted repressive KLF5 corepressors NCoR SnoN. Conversely, DNMT inhibition with SGI-1027 reversed hypermethylation, ferroptotic osteoporosis. In cultured primary cells, ferric ammonium citrate (FAC) mimicking loading similarly induced osteoblasts but osteoclasts, which were rescued siRNA-mediated individual knockdown 1/3a/3b. Intriguingly, alleviated changes caused FAC, inactivator RSL3. More importantly, generated strain osteoblast-specific haplo-deficient Ob+/− developed spontaneous more severe alterations after Ovx operation, showed inactivation RSL3 or semi-knockout largely abolished osteoprotective effects SGI-1027. Taken together, our data suggest epigenetic aberration resulting osteoblastic contribute significantly to pathogenesis, strategies preserving intervention potentially effective treat related disorders.
Language: Английский
Citations
3
Aging Clinical and Experimental Research, Journal Year: 2024, Volume and Issue: 36(1)
Published: June 21, 2024
The Single Point Insulin Sensitivity Estimator (SPISE) index is a surrogate marker for insulin sensitivity. Given the emerging role of bone as an active endocrine organ, its associations with non-invasive measures extra-skeletal functions such sensitivity warrant investigation.
Language: Английский
Citations
2
Biochemical Pharmacology, Journal Year: 2022, Volume and Issue: 207, P. 115377 - 115377
Published: Dec. 10, 2022
Language: Английский
Citations
12