Decreased levels of the gelsolin plasma isoform in patients with rheumatoid arthritis

Osborn, Teresia; Verdrengh, Margareta; Stossel, Thomas P.; Tarkowski, Andrej; Bokarewa, Maria

doi:10.1186/ar2520

Cited by 89 publications

(92 citation statements)

References 46 publications

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“…analyses of the synovial fluids of those patients show consumption of pGSN into the inflamed joints (52). The modulatory functions of GSN we identified on chondrocytes are further supported by the findings that GSN 2/2 mice experience exacerbated arthritis (53).…”

Section: Discussionsupporting

confidence: 65%

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Identification of Novel Chondroprotective Mediators in Resolving Inflammatory Exudates

Kaneva

Greco

Headland

et al. 2017

The Journal of Immunology

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We hypothesized that exudates collected at the beginning of the resolution phase of inflammation might be enriched for tissue protective molecules; thus an integrated cellular and molecular approach was applied to identify novel chondroprotective bioactions. Exudates were collected 6 h (inflammatory) and 24 h (resolving) following carrageenan-induced pleurisy in rats. The resolving exudate was subjected to gel filtration chromatography followed by proteomics, identifying 61 proteins. Fractions were added to C28/I2 chondrocytes, grown in micromasses, ions with or without IL-1β or osteoarthritic synovial fluids for 48 h. Three proteins were selected from the proteomic analysis, α1-antitrypsin (AAT), hemopexin (HX), and gelsolin (GSN), and tested against catabolic stimulation for their effects on glycosaminoglycan deposition as assessed by Alcian blue staining, and gene expression of key anabolic proteins by real-time PCR. In an in vivo model of inflammatory arthritis, cartilage integrity was determined histologically 48 h after intra-articular injection of AAT or GSN. The resolving exudate displayed protective activities on chondrocytes, using multiple readouts: these effects were retained in low m.w. fractions of the exudate (46.7% increase in glycosaminoglycan deposition; ∼20% upregulation of COL2A1 and aggrecan mRNA expression), which reversed the effect of IL-1β. Exogenous administration of HX, GSN, or AAT abrogated the effects of IL-1β and osteoarthritic synovial fluids on anabolic gene expression and increased glycosaminoglycan deposition. Intra-articular injection of AAT or GSN protected cartilage integrity in mice with inflammatory arthritis. In summary, the strategy for identification of novel chondroprotective activities in resolving exudates identified HX, GSN and AAT as potential leads for new drug discovery programs.

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Section: Discussionsupporting

confidence: 65%

“…In analogy to ATT, abundant GSN has been identified in human inflammatory fluids (33,52,55). HX (60 kDa) is primarily produced by hepatocytes, with moderate amounts also synthesized by the nervous system, skeletal muscle, and kidney (56).…”

Section: Discussionmentioning

confidence: 99%

Identification of Novel Chondroprotective Mediators in Resolving Inflammatory Exudates

Kaneva

Greco

Headland

et al. 2017

The Journal of Immunology

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“…The effect of gelsolin shows that this protein assures appropriate cytoskeleton changes, whereas the administration of nucleotides provides aggregation of cells. Our findings are in good agreement with research performed by Ho et al [49,50]. As it was shown the cytoskeletal proteins, actin and vimentin, influence on cellular mechanical properties, thus affecting on mechanical interactions between the chondrocytes and the surrounding tissue matrix.…”

Section: Discussionsupporting

confidence: 94%

The Autologous Gelsolin Combined with Exogenous Nucleotides enhance Chondrogenic Differentiation in Equine Adipose Derived Mesenchymal Stromal Cells - An In Vitro Research

Marędziak¹

2014

J Cell Sci Ther

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“…Plasma gelsolin (pGSN) has been added to the growing list of biomarkers by showing its usefulness in predicting clinical outcomes in acute, severe [4,5,6,7] and chronic diseases [8,9,10,11]. GSN was first identified in cytoplasmic extracts as an actin-scavenger protein, which in the presence of ionized calcium disassembles actin filaments and increases cytosolic fluidity [12,13,14].…”

Section: Introductionmentioning

confidence: 99%

Plasma Gelsolin and Its Association with Mortality and Hospitalization in Chronic Hemodialysis Patients

et al. 2017

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Background: Human plasma gelsolin (pGSN) is an actin-binding protein that is secreted into the extracellular fluid, with the skeletal muscle and myocardial tissues being its major source. Depletion of pGSN has been shown to be related to a variety of inflammatory and clinical conditions. Methods: pGSN levels were prospectively determined in prevalent maintenance hemodialysis (HD) patients from 3 U.S. dialysis centers. Demographics (age, time since dialysis initiation, race, gender, body height and weight, comorbidities), inflammatory markers (C reactive protein, CRP; interleukin 6, IL-6), free triiodothyronine (fT3), and routine laboratory parameters were obtained. We performed Kaplan-Meier and Cox proportional hazard survival analysis for all-cause and cardiovascular mortality, and recurrent event survival analysis for hospitalization. Results: We studied 153 patients; mean age was 60.5 ± 14.7; 52% were males. The mean pGSN level was 6,617 ± 1,789 mU/ml. In univariate analysis, pGSN was positively correlated with body mass index (r = 0.2, p = 0.01), pre-HD serum albumin (r = 0.247, p = 0.002), and pre-HD serum creatinine (r = 0.381, p < 0.001), and inversely with age (r = -0.286, p < 0.001), CRP (r = -0.311, p < 0.001), and IL-6 (r = -0.317, p < 0.001). In the adjusted analysis, the associations with CRP and creatinine were retained. pGSN levels tended to be lower in patients who died (p = 0.08). There was no association with all-cause or cardiovascular mortality, or all-cause hospitalization. Of note, fT3 was lower in patients who died (p = 0.001). Conclusions: Even though pGSN was inversely correlated with age, CRP and IL-6, suggesting that inflammation may influence pGSN, lower pGSN levels were not associated with hospitalization, all-cause and cardio-vascular mortality in this patient population.

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Decreased levels of the gelsolin plasma isoform in patients with rheumatoid arthritis

Cited by 89 publications

References 46 publications

Identification of Novel Chondroprotective Mediators in Resolving Inflammatory Exudates

Identification of Novel Chondroprotective Mediators in Resolving Inflammatory Exudates

The Autologous Gelsolin Combined with Exogenous Nucleotides enhance Chondrogenic Differentiation in Equine Adipose Derived Mesenchymal Stromal Cells - An In Vitro Research

Plasma Gelsolin and Its Association with Mortality and Hospitalization in Chronic Hemodialysis Patients

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