Disturbed glycolipid metabolism activates CXCL13-CXCR5 axis in senescent TSCs to promote heterotopic ossification.
Yuyu ChenJinna WuChipiu WongWenjie GaoXiangdong QiHang ZhouPublished in: Cellular and molecular life sciences : CMLS (2024)
Heterotopic ossification (HO) occurs as a common complication after injury, while its risk factor and mechanism remain unclear, which restricts the development of pharmacological treatment. Clinical research suggests that diabetes mellitus (DM) patients are prone to developing HO in the tendon, but solid evidence and mechanical research are still needed. Here, we combined the clinical samples and the DM mice model to identify that disordered glycolipid metabolism aggravates the senescence of tendon-derived stem cells (TSCs) and promotes osteogenic differentiation. Then, combining the RNA-seq results of the aging tendon, we detected the abnormally activated autocrine CXCL13-CXCR5 axis in TSCs cultured in a high fat, high glucose (HFHG) environment and also in the aged tendon. Genetic inhibition of CXCL13 successfully alleviated HO formation in DM mice, providing a potential therapeutic target for suppressing HO formation in DM patients after trauma or surgery.
Keyphrases
- end stage renal disease
- stem cells
- rna seq
- endothelial cells
- newly diagnosed
- chronic kidney disease
- ejection fraction
- single cell
- high glucose
- peritoneal dialysis
- prognostic factors
- bone marrow
- signaling pathway
- type diabetes
- cell proliferation
- rotator cuff
- insulin resistance
- metabolic syndrome
- adipose tissue
- high fat diet induced
- coronary artery bypass
- atrial fibrillation
- dna damage
- copy number
- percutaneous coronary intervention
- combination therapy
- wild type