Cathepsin G Degrades Synovial Fluid Lubricin: Relevance For Osteoarthritis Pathogenesis
Huang, S.; Thomsson, K. A.; Jin, C.; Alweddi, S.; Struglics, A.; Rolfson, O.; Bjorkman, L. I.; Kalamajsk, S.; Schmidt, T. A.; Jay, G. D.; Krawetz, R.; Karlsson, N. G.; Eisler, T.
Show abstract
Lubricin (PRG4) is a mucin type protein that plays an important role in maintaining normal joint function by providing lubrication and chondroprotection. Improper lubricin modification and degradation has been observed in idiopathic osteoarthritis (OA), while the detailed mechanism still remains unknown. We hypothesized that the protease cathepsin G (CG) may participate in degrading lubricin in synovial fluid (SF). The presence of endogenous CG in SF was confirmed in 16 patients with knee OA. Recombinant human lubricin (rhPRG4) and native lubricin purified from the SF of patients were incubated with exogenous CG and lubricin degradation was monitored using western blot, staining by Coomassie or Periodic Acid-Schiff in gels, and with proteomics. Full length lubricin ([~]300 kDa), was efficiently digested with CG generating a 25-kDa protein fragment, originating from the densely glycosylated mucin domain ([~]250 kDa). The 25-kDa fragment was present in the SF from OA patients, and the amount was increased after incubation with CG. A CG digest of rhPRG4 revealed 135 peptides and 72 glycopeptides, and confirmed that the protease could cleave in different domains of lubricin. Our results suggest that synovial CG may take part in the degradation of lubricin, which could affect the lubrication of OA joints.
Matching journals
The top 9 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- Ex-Vivo Equine Cartilage Explant Osteoarthritis Model - A Metabolomics and Proteomics Study 95%
- Low-invasive sampling method for taxonomic for the identification of archaeological and paleontological bones by proteomics of their collagens 91%
- A mass spectrometry-based atlas of extracellular matrix proteins across 25 mouse organs 91%
Similar papers in this journal
- Multi-omics profiling of collagen-induced arthritis mouse model reveals early metabolic dysregulation via SIRT1 axis 93%
- Rcn3 is Involved in Postnatal Tendon Development by Regulating Collagen Modification and Fibrillogenesis 92%
- Identification of Sensory Fiber Types in Mouse Temporomandibular Joint Tissues 92%
Similar papers in this journal
- Synovial macrophage activation mediates pain experiences in experimental knee osteoarthritis 94%
- Complement factor D (adipsin) mediates pressure-pain hypersensitivity post destabilization of medial meniscus injury 93%
- Development of primary osteoarthritis during aging in genetically diverse UM-HET3 mice 92%
Similar papers in this journal
- Transcriptional response of human articular chondrocytes treated with fibronectin fragments: an in vitro model of the osteoarthritis phenotype 94%
- The recombinant Link module of human TSG-6 suppresses cartilage damage in models of osteoarthritis: a potential disease-modifying OA drug 94%
- BMP signaling: A significant player and therapeutic target for osteoarthritis 94%
Similar papers in this journal
- Aberrant methylation and expression of TNXB promote chondrocyte apoptosis and extracullar matrix degradation in hemophilic arthropathy via AKT signaling 94%
- Down-regulated GAS6 impairs synovial macrophage efferocytosis and promotes obesity-associated osteoarthritis 94%
- Method development and characterization of the low molecular weight peptidome of human wound fluids 94%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.