Role of Cysteine Cathepsins in Joint Inflammation and Destruction in Human Rheumatoid Arthritis and Associated Animal Models

Schurigt, Uta

doi:10.5772/53710

Cited by 3 publications

(2 citation statements)

References 95 publications

(191 reference statements)

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“…by the formation of a pannus which acts to irreparably destroy cartilage and erode the bone (Schurigt 2013). A major misregulation of proteases including metallo-, serine and cysteine proteases appear to be involved in joint destruction as a result of recruitment of immune cells to the site of disease (Firestein, 2005).…”

Section: Autoimmune Diseasesmentioning

confidence: 99%

Cathepsin S: therapeutic, diagnostic, and prognostic potential

Wilkinson

Williams

Scott

et al. 2015

Biological Chemistry

161

139

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Cathepsin S is a member of the cysteine cathepsin protease family. It is a lysosomal protease which can promote degradation of damaged or unwanted proteins in the endo-lysosomal pathway. Additionally, it has more specific roles such as MHC class II antigen presentation, where it is important in the degradation of the invariant chain. Unsurprisingly, mis-regulation has implicated cathepsin S in a variety of pathological processes including arthritis, cancer, and cardiovascular disease, where it becomes secreted and can act on extracellular substrates. In comparison to many other cysteine cathepsin family members, cathepsin S has uniquely restricted tissue expression and is more stable at a neutral pH, which supports its involvement and importance in localised disease microenvironments. In this review, we examine the known involvement of cathepsin S in disease, particularly with respect to recent work indicating its role in mediating pain, diabetes, and cystic fibrosis. We provide an overview of current literature with regards cathepsin S as a therapeutic target, as well as its role and potential as a predictive diagnostic and/or prognostic marker in these diseases.

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Section: Autoimmune Diseasesmentioning

confidence: 99%

Cathepsin S: therapeutic, diagnostic, and prognostic potential

Wilkinson

Williams

Scott

et al. 2015

Biological Chemistry

161

139

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“…Traditionally, cathepsin K has been studied in the context of bone and joint disorders 15 , 28 , 29 . However, there is growing evidence that cathepsin K has a critical role in chronic inflammatory pain signaling.…”

Section: Introductionmentioning

confidence: 99%

Role of cathepsin K in the expression of mechanical hypersensitivity following intra-plantar inflammation

Paracha

Thakar

Darling

et al. 2022

Sci Rep

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Persistent/chronic inflammatory pain involves multiple pathophysiological mechanisms and is far more complex than acute/momentary pain. Current therapeutics for chronic inflammatory pain are often not effective because the etiology responsible for the pain is not addressed by traditional pharmacological treatments. Cathepsin K is a cysteine protease that has mostly been studied in the context of bone and joint disorders. Previous work by others has shown that inhibition of cathepsin K activity reduces osteoarthritis-associated nociception in joints. However, the role of cathepsin K in cutaneous inflammation is understudied. We assessed the effectiveness of genetic deletion or pharmacological inhibition of cathepsin K in male mice on the expression of nocifensive behaviors after formalin injection or mechanical and thermal hypersensitivity after injection of complete Freund’s adjuvant (CFA) into the mouse hind paw. Our data demonstrate that cathepsin K knockout mice (Ctsk−/−) have a reduction in nocifensive behaviors in the formalin test. In addition, Ctsk−/− do not develop mechanical hypersensitivity after CFA injection for up to 7 days. Moreover, we found that inhibition of cathepsin K reduced mechanical hypersensitivity after CFA injection and mRNA levels, protein levels, and cathepsin K activity levels were elevated after CFA injection. Based upon our data, cathepsin K is indicated to play a role in the expression of chemically-induced cutaneous hypersensitivity, as Ctsk−/− mice do not develop mechanical hypersensitivity and show a reduction in nocifensive behaviors. Further research is needed to determine whether attenuating cathepsin K activity may generate a clinically relevant therapeutic.

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Cat’s whiskers (Orthosiphon stamineus) tea modulates arthritis pathogenesis via the angiogenesis and inflammatory cascade

Tabana¹,

Al‐Suede

Ahamed

et al. 2016

BMC Complement Altern Med

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Background Orthosiphon stamineus is used traditionally to treat gout, arthritis, and inflammatory related conditions. The in vitro anti-inflammatory effects of the plant have been scientifically investigated. The goal of the present study was to evaluate the potential of the 50% ethanol extract of O. stamineus (EOS) to treat rheumatoid arthritis.MethodsAnti-arthritic activity was assessed using the in vitro heat denaturation test and the (FCA)-induced arthritis model. Efficacy was assessed by measurements of paw edema and granulation, X-ray radiography, fluorescence molecular tomography (FMT), and histological evaluation. Levels of (TNF-α), interleukin-1 (IL-1), and (COX-1 and COX-2) were analyzed in vitro in lipopolysaccharide (LPS)-stimulated human macrophage (U937). TNF-α and IL-1 levels in the serum samples of arthritic rats were also measured using an ELISA kit.ResultsTreatment with EOS resulted in dose-dependent inhibition of paw edema in acute and chronic models of inflammation. It also inhibited significantly the production of TNF-α, IL-1 COX-1, and COX-2 in the LPS-stimulated U937 macrophages. EOS significantly suppressed FCA-induced paw edema as well as the serum levels of TNF-α and IL-1. X-rays of the synovial joint of the hind leg showed considerable improvement in joint integrity and recovery of tibia-talus bones from degeneration and osteoporotic lesions. Histology of proximal interphalangeal joints of EOS-treated animals showed obvious protection of cartilage and soft tissue. Finally, FMT analysis strongly supported the anti-arthritic effect of EOS. EOS had high phenolic and total flavonoid content as well as strong antioxidant activity.ConclusionsResults illustrated that the anti-arthritic properties of O. stamineus could be beneficial for prevention and management of rheumatoid arthritis and other chronic inflammatory disorders.Graphical abstractIllustration of the Anti- arthritis efficacy of Orthosiphon Stamineus standardized extract.

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Role of Cysteine Cathepsins in Joint Inflammation and Destruction in Human Rheumatoid Arthritis and Associated Animal Models

Cited by 3 publications

References 95 publications

Cathepsin S: therapeutic, diagnostic, and prognostic potential

Cathepsin S: therapeutic, diagnostic, and prognostic potential

Role of cathepsin K in the expression of mechanical hypersensitivity following intra-plantar inflammation

Cat’s whiskers (Orthosiphon stamineus) tea modulates arthritis pathogenesis via the angiogenesis and inflammatory cascade

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