Localization, Shedding, Regulation and Function of Aminopeptidase N/CD13 on Fibroblast like Synoviocytes

Morgan, Rachel L.; Behbahani-Nejad, Nilofar; Endres, Judith; Amin, M. Asif; Lepore, Nick J.; Du, Yuxuan; Urquhart, Andrew G.; Chung, Kevin C.; Fox, David A.

doi:10.1371/journal.pone.0162008

Cited by 20 publications

(32 citation statements)

References 58 publications

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“…This is consistent with the higher APB activity in synovial fluid from swollen knees in a rat model of RA 41 and synovial fluid NAP activity inducing T-cell chemotaxis in a similar animal model. 42 Further, NAP seems to be involved in the pathogenesis of RA 43 and possibly also OA. 29 …”

Section: Discussionmentioning

confidence: 99%

Synovial fluid peptidase activity as a biomarker for knee osteoarthritis clinical progression

Calvo

Sánchez-Herraéz

Casis

et al. 2020

Bone & Joint Research

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Aims To analyze the potential role of synovial fluid peptidase activity as a measure of disease burden and predictive biomarker of progression in knee osteoarthritis (KOA). Methods A cross-sectional study of 39 patients (women 71.8%, men 28.2%; mean age of 72.03 years (SD 1.15) with advanced KOA (Ahlbäck grade ≥ 3 and clinical indications for arthrocentesis) recruited through the (Orthopaedic Department at the Complejo Asistencial Universitario de León, Spain (CAULE)), measuring synovial fluid levels of puromycin-sensitive aminopeptidase (PSA), neutral aminopeptidase (NAP), aminopeptidase B (APB), prolyl endopeptidase (PEP), aspartate aminopeptidase (ASP), glutamyl aminopeptidase (GLU) and pyroglutamyl aminopeptidase (PGAP). Results Synovial fluid peptidase activity varied significantly as a function of clinical signs, with differences in levels of PEP (p = 0.020), ASP (p < 0.001), and PGAP (p = 0. 003) associated with knee locking, PEP (p = 0.006), ASP (p = 0.001), GLU (p = 0.037), and PGAP (p = 0.000) with knee failure, and PEP (p = 0.006), ASP (p = 0.001), GLU (p = 0.037), and PGAP (p < 0.001) with knee effusion. Further, patients with the greatest functional impairment had significantly higher levels of APB (p = 0.005), PEP (p = 0.005), ASP (p = 0.006), GLU (p = 0.020), and PGAP (p < 0.001) activity, though not of NAP or PSA, indicating local alterations in the renin-angiotensin system. A binary logistic regression model showed that PSA was protective (p = 0.005; Exp (B) 0.949), whereas PEP (p = 0.005) and GLU were risk factors (p = 0.012). Conclusion These results suggest synovial fluid peptidase activity could play a role as a measure of disease burden and predictive biomarker of progression in KOA. Cite this article: Bone Joint Res 2020;9(11):789–797.

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Section: Discussionmentioning

confidence: 99%

Synovial fluid peptidase activity as a biomarker for knee osteoarthritis clinical progression

Calvo

Sánchez-Herraéz

Casis

et al. 2020

Bone & Joint Research

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“…Indeed, Ab-mediated cross-linking of CD13 in mast cells leads to IL-6 production (82). Additionally, soluble CD13 is highly abundant in synovial fluid of rheumatoid arthritis patients, where it increases expression of proinflammatory cytokines (83)(84)(85)(86)(87)(88)(89)(90). With regard to HCoV-229E infection, treatment of primary human nasal and tracheal epithelial cells with glycopyrronium/formoterol/budesonide, a mixture of drugs used to treat chronic obstructive pulmonary disease caused by HCoV-229E infection, led to reduced CD13 expression, fewer acidic endosomes that are essential for the entry of HCoV-229E, as well as decreased production of inflammatory cytokines (79).…”

Section: Cd13/apn/anpep Inflammation and Il-6mentioning

confidence: 99%

Coronavirus Receptors as Immune Modulators

Devarakonda

Meredith

Ghosh

et al. 2021

The Journal of Immunology

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The Coronaviridae family includes the seven known human coronaviruses (CoV) that cause mild to moderate respiratory infections (HCoV-229E, HCoV-NL63, HCoV-OC43, HCoV-HKU1) as well as severe illness and death (MERS-CoV, SARS-CoV, SARS-CoV-2). Severe infections induce hyperinflammatory responses that are often intensified by host adaptive immune pathways to profoundly advance disease severity. Proinflammatory responses are triggered by CoV entry mediated by host cell surface receptors. Interestingly, five of the seven strains use three cell surface metallopeptidases (CD13, CD26, and ACE2) as receptors, whereas the others employ O-acetylated-sialic acid (a key feature of metallopeptidases) for entry. Why CoV evolved to use peptidases as their receptors is unknown, but the peptidase activities of the receptors are dispensable, suggesting the virus uses/benefits from other functions of these molecules. Indeed, these receptors participate in the immune modulatory pathways that contribute to the pathological hyperinflammatory response. This review will focus on the role of CoV receptors in modulating immune responses.

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“…Another example of a catabolic protein carried by EVs is Aminopeptidase N/CD13. This metalloproteinase is found in EVs and can be increased in RA synovium and synovial fluid via transport by EVs [45]. Inhibition of CD13 results in decreased growth and migration of fibroblast like synoviocytes, meaning that CD13 may have a role in the hyperplasia that creates pathology in RA [45].…”

Section: Extracellular Vesicles In Degenerative Joint Diseases: Rheummentioning

confidence: 99%

Emerging role of extracellular vesicles in musculoskeletal diseases

Murphy

Withrow

Hunter

et al. 2018

Molecular Aspects of Medicine

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Research into the biology of extracellular vesicles (EVs), including exosomes and microvesicles, has expanded significantly with advances in EV isolation techniques, a better understanding of the surface markers that characterize exosomes and microvesicles, and greater information derived from -omics approaches on the proteins, lipids, mRNAs, and microRNAs (miRNAs) transported by EVs. We have recently discovered a role for exosome-derived miRNAs in age-related bone loss and osteoarthritis, two conditions that impose a significant public health burden on the aging global population. Previous work has also revealed multiple roles for EVs and their miRNAs in muscle regeneration and congenital myopathies. Thus, EVs appear to be involved in a number of degenerative conditions that impact the musculoskeletal system, indicating that the musculoskeletal system is an excellent model for investigating the role of EVs in tissue maintenance and repair. This review highlights the role of EVs in bone, skeletal muscle, and joint health, including both normal tissue metabolism as well as tissue injury repair and regeneration. A consistent theme that emerges from study of musculoskeletal EVs is that various miRNAs appear to mediate a number of key pathological processes. These findings point to a potential therapeutic opportunity to target EV-derived miRNAs as a strategy for improving musculoskeletal function.

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Localization, Shedding, Regulation and Function of Aminopeptidase N/CD13 on Fibroblast like Synoviocytes

Cited by 20 publications

References 58 publications

Synovial fluid peptidase activity as a biomarker for knee osteoarthritis clinical progression

Synovial fluid peptidase activity as a biomarker for knee osteoarthritis clinical progression

Coronavirus Receptors as Immune Modulators

Emerging role of extracellular vesicles in musculoskeletal diseases

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