Bioactive Materials, Journal Year: 2025, Volume and Issue: 51, P. 333 - 382
Published: May 19, 2025
Language: Английский
Journal of Translational Medicine, Journal Year: 2025, Volume and Issue: 23(1)
Published: April 11, 2025
Language: Английский
Citations
1
Cellular Signalling, Journal Year: 2025, Volume and Issue: unknown, P. 111758 - 111758
Published: March 1, 2025
Language: Английский
Citations
0
Journal of Biological Chemistry, Journal Year: 2025, Volume and Issue: unknown, P. 108500 - 108500
Published: April 1, 2025
Language: Английский
Citations
0
Bone Research, Journal Year: 2025, Volume and Issue: 13(1)
Published: April 11, 2025
Abstract Neural EGFL-like 2 (NELL2) is a secreted protein known for its regulatory functions in the nervous and reproductive systems, yet role bone biology remains unexplored. In this study, we observed that NELL2 was diminished of aged ovariectomized (OVX) mice, as well serum osteopenia osteoporosis patients. vitro loss-of-function gain-of-function studies revealed facilitated osteoblast differentiation impeded adipocyte from stromal progenitor cells. vivo further demonstrated deletion preosteoblasts resulted decreased cancellous mass mice. Mechanistically, interacted with FNI-type domain located at C-terminus Fibronectin 1 (Fn1). Moreover, found activated focal adhesion kinase (FAK)/AKT signaling pathway through Fn1/integrin β1 (ITGB1), leading to promotion osteogenesis inhibition adipogenesis. Notably, administration NELL2-AAV ameliorate loss OVX These findings underscore significant homeostasis, suggesting potential therapeutic target managing osteoporosis.
Language: Английский
Citations
0
Frontiers in Endocrinology, Journal Year: 2025, Volume and Issue: 16
Published: April 24, 2025
Lipid metabolic disorder (LMD) serves as a systemic driver of osteoporosis (OP), with jawbone (JOP) representing clinically significant yet underexplored complication. Current clinical treatments for JOP remain suboptimal, highlighting the need innovative approaches. The use regulators represents promising therapeutic strategy OP management. While brown adipose tissue-derived extracellular vesicles (BEV) exhibit regulatory potential, their capacity to mitigate LMD-associated remains unclear. A high-fat diet (HFD)-induced LMD mouse model was established identify phenotype through micro-computed tomography (micro-CT) and transcriptomic profiling. BEV isolation optimized using liberase enzyme-enhanced differential centrifugation, in vivo tracking confirming biodistribution. In vitro, effects on hepatocytes were assessed triglyceride (TG) content, free fatty acid (FFA) levels, mitochondrial function. additional benefits osteogenic microenvironment evaluated via AML12/MC3T3-E1 indirect co-culture under high-lipid conditions. Dual validated phenotyping, micro-CT histomorphometry analysis. Sixteen weeks HFD successfully induced typical manifestations mice. Transcriptomic sequencing revealed downregulation osteogenic-related genes concomitant upregulation lipid metabolism-associated showed exogenous predominantly accumulated liver rather than jawbone. treatment significantly reduced intracellular TG FFA content hepatocytes, while enhancing activity MC3T3-E1 cells co-culture. Mitochondrial analyses that effectively increased proportion active mitochondria, reactive oxygen species (ROS) generation rate, enhanced consumption rate (OCR) hepatocytes. Biochemical assay cage testing lower level along improved fat utilization thermogenesis BEV-treated Micro-CT immunofluorescence staining further confirm improvements mice regarding bone volume fraction, trabecular number, thickness, separation, RUNX2 expression. This study establishes crucial factor identifies BEV-mediated transferring LMD-related JOP.
Language: Английский
Citations
0
Stem Cell Research & Therapy, Journal Year: 2025, Volume and Issue: 16(1)
Published: May 5, 2025
Recent studies have suggested that targeting senescent cells in joint tissues may alleviate osteoarthritis (OA) progression. However, this strategy encounters significant challenges, partially due to the high degree of cellular heterogeneity osteoarthritic tissues. Moreover, little information is available on role skeletal stem cell (SSC) senescence, as compared differentiated cells, OA In study, single-cell RNA sequencing (scRNA-seq) articular cartilages and subchondral bones knee joints mice with post-traumatic (PTOA) were performed. Further vivo vitro performed reveal mechanisims SSCs during development lesions progression by microCT, pathological analysis, functional gain loss experiments. The one-way ANOVA was used multiple group data analysis. scRNA-seq demonstrated leptin receptors (Lepr) positive underwent senescence addition, leptin-Lepr signaling pathway induced signal transducer activator transcription 3 (STAT3) expression SSCs, which consequently augmented fibroblast growth factor 7 (FGF7). analyses revealed FGF7 exacerbated abnormal bone remodeling enhancing formation suppressing resorption. analysis osteogenic differentiation but inhibited osteoclastogenesis a concentration-dependent manner. summary, our findings demonstrate promotes SSC exacerbates activating STAT3-FGF7 axis progression, shed light novel therapeutic strategies for OA.
Language: Английский
Citations
0
Bioactive Materials, Journal Year: 2025, Volume and Issue: 51, P. 333 - 382
Published: May 19, 2025
Language: Английский
Citations
0