Modulation of Superficial Zone Protein/Lubricin/PRG4 by Kartogenin and Transforming Growth Factor-β1 in Surface Zone Chondrocytes in Bovine Articular Cartilage

Miyatake, Kazumasa; Iwasa, Kenjiro; McNary, Sean M.; Peng, Gordon; Reddi, A. Hari

doi:10.1177/1947603516630789

Cited by 21 publications

(16 citation statements)

References 40 publications

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“…The frequency (%) of samples containing the given citrullinated protein is shown. ( f ) The relationships of the extracellular citrullinated proteins to selected biological processes according to the GO Database 6/2014 release 45 appended with current knowledge of the biological role of angiogenin 46 – 48 , MXRA5 49 , PRG4 50 and EFEMP1 51 . IGHM, which is a subunit of IgM is connected to inflammatory response.…”

Section: Resultsmentioning

confidence: 99%

Joint inflammation related citrullination of functional arginines in extracellular proteins

Sipilä

Ranga

Rappu

et al. 2017

Sci Rep

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We report the extent, specific sites and structural requirements of joint inflammation related citrullination in extracellular proteins. A total of 40 synovial fluid samples derived from chronically inflamed human joints were analysed by heparin-agarose fractionation and LC-MS/MS. Citrullination of 55 arginines in extracellular proteins was detected. Importantly, 20% of the sites have a characterized function related to the hallmarks of destructive joint inflammation. E.g. four arginine residues, shown here to be citrullinated, are also affected by mutations in inherited diseases causing haemolysis or blood clotting dysfunction. Citrullination of integrin ligands was selected for further studies since fibronectin R234 in isoDGR was among the most frequently citrullinated arginines in synovial fluid. Assays with synovial fibroblasts and integrin αVβ3 indicated decreased affinity to the enzymatically citrullinated integrin binding sites. To conclude, our data indicate that in inflamed joints extensive citrullination affects the functional arginine residues in extracellular proteins.

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Section: Resultsmentioning

confidence: 99%

Joint inflammation related citrullination of functional arginines in extracellular proteins

Sipilä

Ranga

Rappu

et al. 2017

Sci Rep

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“…The effect of KGN on lubricin synthesis was also investigated in a couple of following studies. 11,12 Liu et al investigated the expression and secretion of lubricin in bone marrow stem cells (BMSCs) treated with different combinations of TGF-b1, BMP-7, and/or KGN. Lubricin protein and mRNA levels were highest in BMSCs treated with all three factors: TGF-b1, BMP-7, and KGN.…”

Section: Action Mechanism Of Kgnmentioning

confidence: 99%

“…KGN had no significant effect on altering SZP synthesis in superficial zone chondrocytes cultured in monolayer, micromass, and explant culture or in synoviocytes under no cytokine or under cytokines (TGF-b1 or IL-1b). 12 KGN may exert more effect by blocking degradation than by stimulating repair. Ono et al investigated the chondroprotective effect of KGN on the retention of hyaluronate (HA)dependent pericellular matrices as well as other CD44-HA interactions that are necessary for the maintenance of articular chondrocytes.…”

Section: Action Mechanism Of Kgnmentioning

confidence: 99%

Application of kartogenin for musculoskeletal regeneration

2017

J Biomedical Materials Res

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Kartogenin (KGN) is a recently characterized small molecule that promotes the selective differentiation of mesenchymal stem cells into chondrocytes, and thus, KGN stimulates cartilage regeneration. KGN also possess chondro-protective effect. Furthermore, because it is a highly stable small molecule, KGN can be stored and transported at room temperature. These obvious superiorities over peptide growth factors make KGN a desirable chondrogenic agent for cartilage regeneration. Since its discovery, KGN has drawn much attention as a new chondrogenic drug for intraarticular (IA) treatment. Although it was originally developed with a focus on OA, it has been used to treat other conditions and to promote disc and bone-tendon junction regeneration. Our group has also developed several formulations for IA delivery of KGN including KGN-conjugated chitosan nano/microparticles, thermo-responsive polymeric nanospheres based on chitosan oligosaccharide conjugated pluronic F127, and hyluronate hydrogels containing polyethylene glycol (PEG/KGN) micelles. This review was undertaken to summarize current research on the action mechanism of KGN and the various formulations described in the literature that induce musculoskeletal regeneration. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 1141-1148, 2018.

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“…These two components contribute to building the structure of cartilage. In addition, proteoglycan 4 (PRG4 or lubricin) is a kind of PRG observed on the surface of articular cartilage and acts as a joint or boundary lubricant . Although the total volume of PRG4 is small, it is functionally important in cartilage.…”

Section: Introductionmentioning

confidence: 99%

Estrogen reverses nicotine‐induced inflammation in chondrocytes via reducing the degradation of ECM

et al. 2019

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Problem: Osteoarthritis (OA) is a chronic disease with a very high incidence and the pathology of which is quite complex. Epidemiological investigation showed that OA may be related to smoking and estrogen levels, but there are few studies focused on the cross-effect of these two factors. This research aims to investigate the molecular mechanism of nicotine and estrogen effects on chondrocytes to study the effect of smoking on the incidence of osteoarthritis in women. Method of the study:Nicotine was added to obtain inflammatory supernatants of macrophages, which were used to induce chondrocyte inflammation. Toluidine staining and immunohistochemistry were used to detect the extracellular matrix (ECM) of chondrocytes, while the important proteins in the metabolism of chondrocytes were detected by Western blot. Results: Nicotine-induced inflammatory supernatant promoted the degradation of ECM, such as type II collagen, aggrecan and proteoglycan 4. While in the presence of physiological concentrations of estrogen, this destructive effect is reversed. On the molecular level, estrogen (17β-estradiol, 1 nmol/L) can inhibit the matrix degrading enzymes and promote the transforming growth factor (TGF)-β1 pathway which is involved in matrix synthesis. However, in the presence of inflammatory induction, although estrogen could still inhibit the expression of matrix degrading enzymes, it inhibited the TGF-β1 pathway. Moreover, the different inflammatory factors in the inflammatory supernatant, mainly tumor necrosis factor-α, interleukin-1β, had different effects on the metabolic processes of chondrocytes. Conclusion: Estrogen reverses nicotine-induced inflammation mainly via reducing the degradation of ECM. The cross-effect of estrogen and inflammatory factor inhibitors can be a potential clinical reference for OA patients. K E Y W O R D S chondrocytes, estrogen, extracellular matrix, nicotine, osteoarthritis | INTRODUC TI ONOsteoarthritis (OA) is one of the most common chronic, degenerative joint inflammations which can worldwide cause severe disabilities. 1 The pathology of this disease is very complex. Previous studies have found that estrogen is an important influencing factor that can inhibit the development of OA. 2 Recent studies also show that smoking has a certain impact on the occurrence of OA, but the specific mechanism is controversial. 3

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Modulation of Superficial Zone Protein/Lubricin/PRG4 by Kartogenin and Transforming Growth Factor-β1 in Surface Zone Chondrocytes in Bovine Articular Cartilage

Cited by 21 publications

References 40 publications

Joint inflammation related citrullination of functional arginines in extracellular proteins

Joint inflammation related citrullination of functional arginines in extracellular proteins

Application of kartogenin for musculoskeletal regeneration

Estrogen reverses nicotine‐induced inflammation in chondrocytes via reducing the degradation of ECM

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