scholarly journals SERUM LEVEL OF MMP-3 IN PATIENTS WITH PSORIATIC ARTRITIS TREATED WITH TNF-α BLOKERS

2019 ◽  
Vol 34 (4) ◽  
pp. 939-941
Author(s):  
Stanislava Popova ◽  
Mariela Geneva-Popova ◽  
Anastas Batalov
Keyword(s):  
Extracellular Matrix ◽  
Serum Level ◽  
Disease Activity ◽  
Proteolytic Enzymes ◽  
Degenerative Joint Disease ◽  
Joint Disease ◽  
Blocker Therapy ◽  
Tnf Α ◽  
Extracellular Matrix Components ◽  
The Mean

Background: Matrix metalloproteinases (MMPs) are a family of proteolytic enzymes whose primary function is to break down the extracellular matrix. MMPs are important for tissue remodeling and affect cell signaling. MMP-3 (Stromelysin-1, Transin-1) hydrolyzes natural collagen and extracellular matrix components such as proteoglycan, laminin, fibronectin, gelatin and collagen type III, IV and IX and activates the precursor of IL1-beta. Psoriatic arthritis (PsA) is a rapidly developing, debilitating disease, and it is important for patients with it to identify serum biomarkers to predict its development. Patients and Methods: MMP-3 has been studied in 21 patients with PsA, 16 patients with PsA receiving TNF-α blocker therapy, and 22 patients with gonarthrosis and 15 healthy age-matched adults. All patients were treated and monitored at the University Clinic of Rheumatology, UMHAT “Kaspela“ and UMHAT “Steti Georgi”, Medical University, Plovdiv. The study of MMPs was performed using an ELISA methodology. Statistical processing of the data was performed using the SPSS 23 program with confidence (p <0.001). Results: The mean MMP-3 value in patients with PsA was 197.00 ± 35.90 pg / ml, in patients with AS 101.08 ± 15.76 ng / ml. The mean MMP-3 in patients with PsA receiving TNF-α blocker therapy and with low clinical disease activity was 50.48 ± 9.22 ng / ml. The mean MMP-3 in patients with gonarthrosis was 42.91 ± 11.72 ng / ml. The mean MMP-3 values in patients with active PsA were significantly different from those treated with TNF-α-blockers and patients with degenerative joint disease and controls (p <0.05). Conclusion: MMP-3 was significantly increased in patients with PsA compared with patients with osteoarthritis and healthy subjects. Administration of TNF-α blockers gradually leads to a decrease in the serum level of MMP-3 and can serve as a biomarker for disease activity as well as for evaluating the effect of therapy. arthrosis disease

scholarly journals Long Noncoding RNA CIR Promotes Chondrocyte Extracellular Matrix Degradation in Osteoarthritis by Acting as a Sponge For Mir-27b

2017 ◽  
Vol 43 (2) ◽  
pp. 602-610 ◽  
Author(s):  
Yu-Fei Li ◽  
Shu-Hua Li ◽  
Yong Liu ◽  
Ya-Tong Luo
Keyword(s):  
Extracellular Matrix ◽  
Noncoding Rna ◽  
Mrna Level ◽  
Cartilage Degradation ◽  
Degenerative Joint Disease ◽  
Cellular Level ◽  
Joint Disease ◽  
Small Interfering Rnas ◽  
Tnf Α ◽  
Regulatory Functions

Background/Aims: Osteoarthritis (OA) is a degenerative joint disease characterized by articular cartilage degradation. The degradation of the extracellular matrix (ECM) of chondrocyte is closely associated with the destruction of joints in OA patients. lncRNAs are non-coding segments of RNA that possess important regulatory functions at the cellular level and in a variety of pathophysiological processes. The present study was conducted to investigate whether lncRNA-CIR regulated the expression of MMP13 as a sponge of miR-27 in OA. Methods: Primary cultured chondrocytes were challenged by IL-1β and TNF-α to simulate OA conditions. qRT-PCR was performed to detect the miR-27, lncRNA-CIR, MMP13 mRNA expression levels. Western blot was applied to detect MMP13 protein expression. Soluble sGAG secretion/ formation was analysed by the dimethylmethylene blue (DMMB) assay. lncRNA-CIR overexpression or inhibition was performed using overexpression plasmid and small interfering RNAs (siRNAs), respectively. Results: lncRNA-CIR significantly up-regulated in OA patients, concomitantly down-regulated miR-27 and up-regulated MMP13. Bioinformatics analysis predicted miR-27 was the target of both lncRNA-CIR and MMP13. Overexpression of lncRNA-CIR significantly increased the expression of MMP13, while miR-27 remarkably suppressed the expression of MMP13, Accompanying with the increases of mRNA level, protein level and relative luciferase activity. Conclusion: The present findings indicated that lncRNA-CIR/miR-27/MMP13 axis involved in the degradation of the ECM of chondrocyte in OA.

Osteotomy for Correction of Premature Growth Plate Closure in 24 Dogs

1994 ◽  
Vol 07 (03) ◽  
pp. 129-135 ◽  
Author(s):  
C.W. Miller ◽  
P.W. Morgan
Keyword(s):  
Corrective Osteotomy ◽  
Functional Results ◽  
Degenerative Joint Disease ◽  
Joint Disease ◽  
Angular Deformity ◽  
Dynamic Correction ◽  
Age At Surgery ◽  
Limb Deformities ◽  
The Mean ◽  
A Prospective Study

SummaryTwenty-four dogs (27 limbs) were evaluated after surgery for correction of forelimb angular limb deformities. Partial ulnar ostectomies or definitive corrective osteotomies were performed depending upon the age of the dog. According to owner assessment nine of fourteen limbs were considered functionally good, or excellent, after partial ulnar ostectomies. Younger dogs appeared to have better functional results after dynamic correction with the mean age at surgery of dogs with good to excellent results being 6.5 months contrasted to the mean age at surgery of dogs with fair to poor results being 9.75 months. Ten of fourteen limbs were considered functionally good or excellent after definitive corrective osteotomy. One dog had definitive osteotomy after partial ulnar ostectomy in order to further correct a residual angular deformity. However, 58% of the limbs with radiographic follow-up had signs of degenerative joint disease (DJD). There were not significant differences between neither degree of angulation remaining after surgery and the functional result nor the degree of angulation remaining after surgery and the development of DJD. A prospective study is warranted to more objectively assess the efficacy of surgical correction of angular limb deformities in dogs.Twenty-four dogs were evaluated after surgery for correction of forelimb angular limb deformities. The results are described.

scholarly journals Andrographis paniculata Extract Relieves Pain and Inflammation in Monosodium Iodoacetate-Induced Osteoarthritis and Acetic Acid-Induced Writhing in Animal Models

Processes ◽  
2020 ◽  
Vol 8 (7) ◽  
pp. 873
Author(s):  
Donghun Lee ◽  
Chae Yun Baek ◽  
Ji Hong Hwang ◽  
Mi-Yeon Kim
Keyword(s):  
Acetic Acid ◽  
Weight Bearing ◽  
Cartilage Damage ◽  
Degenerative Joint Disease ◽  
Andrographis Paniculata ◽  
Joint Disease ◽  
Tnf Α ◽  
Monosodium Iodoacetate ◽  
History Of

Osteoarthritis (OA), being the most prominent degenerative joint disease is affecting millions of elderly people worldwide. Although Andrographis paniculata is an ethnic medicine with a long history of being used as analgesic agent, no study using a monosodium iodoacetate (MIA) model has investigated its potential activities against OA. In this study, experimental OA was induced in rats with a knee injection of MIA, which represents the pathological characteristics of OA in humans. A. paniculata extract (APE) substantially reversed the loss of hind limb weight-bearing and the cartilage damage resulted from the OA induction in rats. Additionally, the levels of serum pro-inflammatory cytokines, such as IL-1β, IL-6, and TNF-α as well as the concentration of matrix metalloproteinases, including MMP-1, MMP-3, MMP-8, and MMP-13 were decreased by APE administration. Acetic acid-induced writhing responses in mice which quantitatively measure pain were significantly reduced by APE. In vitro, APE inhibited the generation of NO and downregulated the expression of IL-1β, IL-6, COX-2, and iNOS in lipopolysaccharide (LPS)-stimulated RAW264.7 cells. The above results suggest the potential use APE as a therapeutic agent against OA.

LncRNA MEG3 Inhibits the Degradation of the Extracellular Matrix of Chondrocytes in Osteoarthritis via Targeting miR-93/TGFBR2 Axis

Cartilage ◽  
2019 ◽  
pp. 194760351985575 ◽  
Author(s):  
Kang Chen ◽  
Hao Zhu ◽  
Min-Qian Zheng ◽  
Qi-Rong Dong
Keyword(s):  
Extracellular Matrix ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Cartilage Degradation ◽  
Degenerative Joint Disease ◽  
Joint Disease ◽  
Regulatory Function ◽  
Qrt Pcr ◽  
Ecm Degradation ◽  
Competitive Endogenous Rna

Background As a degenerative joint disease, osteoarthritis (OA) is characterized by articular cartilage degradation. Long noncoding RNAs (lncRNAs) act critical roles in the regulation of OA development, including affecting the proliferation, apoptosis, extracellular matrix (ECM) degradation, and inflammatory response of chondrocytes. The current study’s aim was to investigate the regulatory function and the underlying molecular mechanism of lncRNA MEG3 in ECM degradation of chondrocytes in OA. Methods In the current study, chondrocytes were induced by interleukin-1β (IL-1β) to simulate OA condition, and further assessed cell viability, lncRNA MEG3 and miR-93 expression levels. Overexpression or knockdown of lncRNA MEG3 in chondrocytes treated with IL-1β were performed to investigate the function of MEG3 in regulating cell proliferation, apoptosis and ECM degradation using EdU assay, flow cytometry, quantitative reverse transcription polymerase chain reaction (qRT-PCR), and Western blot. The interaction between MEG3 and miR-93 was assessed using qRT-PCR. Furthermore, overexpression of miR-93 was performed as recovery experiment to explore the functional mechanism of MEG3. Results MEG3 was significantly downregulated in chondrocytes treated with IL-1β, whereas miR-93 was upregulated concomitantly. Overexpression of MEG3 induced the proliferation, suppressed the apoptosis, and relieved the degradation of ECM in IL-1β-induced chondrocytes. By contrast, knockdown of MEG3 suppressed the proliferation, promoted the apoptosis, and aggravated ECM degradation in IL-1β induced chondrocytes. In addition, MEG3 was found to relieve the inhibitive expression of TGFBR2 as a competitive endogenous RNA (ceRNA) of miR-93, and then activated transforming growth factor-β (TGF-β) signaling pathway, regulated chondrocytes ECM degradation in IL-1β induced chondrocytes subsequently. Conclusion LncRNA MEG3 targeted miR-93/TGFBR2 axis, regulated the proliferation, apoptosis and ECM degradation of chondrocytes in OA.

Levels of Plasma-soluble Triggering Receptor Expressed on Myeloid Cells-1 (sTREM-1) Are Correlated with Disease Activity in Rheumatoid Arthritis

2012 ◽  
Vol 39 (5) ◽  
pp. 933-938 ◽  
Author(s):  
SANG TAE CHOI ◽  
EUN-JIN KANG ◽  
YOU JUNG HA ◽  
JUNG-SOO SONG
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Myeloid Cells ◽  
Disease Status ◽  
Joint Disease ◽  
Healthy Controls ◽  
Cell Counts ◽  
Tnf Α ◽  
White Blood Cell Counts ◽  
Factor Α

Objective.To determine whether levels of plasma-soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) are elevated in patients with rheumatoid arthritis (RA) and whether levels are correlated with disease activity and other variables.Methods.Our study included 71 patients with RA and 50 age- and sex-matched healthy controls. Clinical characteristics and laboratory measures, including erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and 28-joint Disease Activity Score (DAS28) were assessed. Plasma levels of sTREM-1 and tumor necrosis factor-α (TNF-α) were measured by ELISA.Results.Patients with RA had significantly higher plasma sTREM-1 levels than healthy controls (170.10 ± 84.71 pg/ml vs 97.41 ± 40.64 pg/ml; p < 0.001). In patients with RA, plasma sTREM-1 levels were found to be correlated with DAS28, ESR, CRP, white blood cell counts, neutrophil counts, and plasma TNF-α levels (r = 0.329, p = 0.005; r = 0.241, p = 0.043; r = 0.314, p < 0.001; r = 0.261, p = 0.028; r = 0.278, p = 0.019; and r = 0.313, p = 0.009, respectively). Plasma sTREM-1 levels in patients with active disease status (DAS28 > 3.2) were significantly higher than in those with low disease status (DAS28 ≤ 3.2; 208.89 ± 100.14 pg/ml vs 150.29 ± 68.70 pg/ml; p = 0.005).Conclusion.Patients with RA had higher plasma sTREM-1 levels than healthy controls, and plasma sTREM-1 levels were correlated with disease activity measures, suggesting that plasma sTREM-1 could play a role in the inflammatory process associated with TNF-α, and that it may be a useful disease activity marker in RA.

Chondroitin - application in the treatment of degenerative joint disease

2016 ◽  
Vol 18 (6) ◽  
pp. 621-628 ◽  
Author(s):  
Wiesław Tomaszewski
Keyword(s):  
Molecular Level ◽  
Proteolytic Enzymes ◽  
Chondroitin Sulphate ◽  
Cartilage Degradation ◽  
Degenerative Joint Disease ◽  
Joint Disease ◽  
Chondrocyte Apoptosis ◽  
Structural Elements ◽  
Acid Biosynthesis ◽  
Physiological Processes

Chondroitin is an organic compound, belonging to the group of glycosaminoglycans. In the treatment of degenerative joint disease, aka osteoarthritis, chondroitin sulphate is applied as a medicine or a dietary supplement. The biological importance of chondroitin sulphate has been already largely determined. The newest data on glycobiology research suggest that proteoglycans, as well as their complex polysaccharide macroparticles not only are the structural elements, but also they participate in multiple metabolic processes at a molecular level as well as in the physiological processes, regulating this type of mechanisms. The preparations applied in the treatment of degenerative joint disease, containing chondroitin sulphate, are attributed numerous therapeutic and chondroprotective properties including stabilizing synthesis processes and cartilage degradation through stimulation and inhibition of chondrocyte apoptosis (production of the elements of the intracellular substance and osteocyte stimulation), an increased proteoglycan and hyaluronic acid biosynthesis, inhibition of the activity of proteolytic enzymes and hyaluronidase, reduction of inflammatory mediators (prostaglandins and leukotrienes) and a decreased collagen II degradation. Based on the results of the multidirectional research available in the newest source literature, the analysis of the therapeutic efficacy and safety of chondroitin application in the treatment of degenerative joint disease was conducted.

Minimal Disease Activity and Remission in Psoriatic Arthritis Patients Treated with Anti-TNF-α Drugs

2015 ◽  
Vol 43 (2) ◽  
pp. 350-355 ◽  
Author(s):  
Fabio Massimo Perrotta ◽  
Antonio Marchesoni ◽  
Ennio Lubrano
Keyword(s):  
Clinical Practice ◽  
Psoriatic Arthritis ◽  
Disease Activity ◽  
Health Assessment ◽  
Joint Disease ◽  
Practice Setting ◽  
Minimal Disease Activity ◽  
Tnf Α ◽  
Clinical Practice Setting ◽  
Minimal Disease

Objective.A state of remission is the target of therapy in chronic arthritis. The aim of the present study was to assess the rate of minimal disease activity (MDA) and remission in patients with psoriatic arthritis (PsA) treated with tumor necrosis factor (TNF-α) blockers. Disease characteristics and predictors of MDA were also evaluated.Methods.Patients fulfilling the ClASsification for Psoriatic ARthritis (CASPAR) criteria and treated with TNF-α blockers adalimumab, etanercept, or golimumab were enrolled and prospectively followed every 4 months for 1 year in a clinical practice setting. Patients were considered in MDA when they met at least 5/7 of the criteria previously defined. Other remission criteria evaluated were 28-joint Disease Activity Score-C-reactive protein (DAS28-CRP) < 2.6 and Disease Activity in Psoriatic Arthritis (DAPSA) score ≤ 3.3. Patients achieving MDA were compared to non-MDA to identify outcome predictor factors.Results.Of the 75 patients treated with TNF-α blockers, at baseline no patients were in MDA or had a DAPSA score ≤ 3.3, while 25 (21.3%) had a DAS28-CRP score < 2.6. Five patients (6%) discontinued treatment because of side effects or inefficacy during followup. After 12 months, MDA was achieved in 46 patients (61.3%). No difference was found among the 3 anti-TNF-α drugs. Predictors for MDA were found to be male sex, high CRP, high erythrocyte sedimentation rate, and low Health Assessment Questionnaire.Conclusion.In our prospective observational study, based on a clinical practice setting, MDA was achieved in 61.3% of patients treated with TNF-α blockers, identifying this as an achievable target for patients with PsA. Predictors of remission were also identified.

Clinical Evaluation and Long-Term Follow-Up of Dogs Having Coronoidectomy for Elbow Incongruity

2003 ◽  
Vol 39 (5) ◽  
pp. 473-478 ◽  
Author(s):  
Margaret Puccio ◽  
Dominic J. Marino ◽  
Joseph D. Stefanacci ◽  
Brian McKenna
Keyword(s):  
Degenerative Joint Disease ◽  
Joint Disease ◽  
Disease Entity ◽  
Radiographic Findings ◽  
Clinical Presentations ◽  
Long Term Follow Up ◽  
The Mean ◽  
Joint Incongruity

A retrospective study was performed describing the clinical presentations, radiographic findings, and surgical outcomes of 17 dogs (18 elbows) following medial coronoidectomy for the treatment of elbow joint incongruity as a sole disease entity. Complete resolution of lameness was achieved in 100% of the cases. The mean radiographic arthrosis grade progressed in 70% of the cases. Results of this study indicate that resolution of clinical lameness may be achieved with medial coronoidectomy in dogs with elbow incongruity; however, progression of degenerative joint disease with unknown, long-term clinical significance can be expected after surgery.

scholarly journals Matrix-targeted Nanoparticles for MMP13 RNA Interference Blocks Post-Traumatic Osteoarthritis

2020 ◽  
Author(s):  
Sean K Bedingfield ◽  
Fang Yu ◽  
Danielle D. Liu ◽  
Meredith A. Jackson ◽  
Lauren E. Himmel ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Rna Interference ◽  
Targeted Delivery ◽  
Degenerative Joint Disease ◽  
Joint Disease ◽  
Specific Cell ◽  
Long Term Treatment ◽  
Post Traumatic ◽  
Mmp13 Expression

AbstractOsteoarthritis (OA) is a debilitating and prevalent chronic disease, but there are no approved disease modifying OA drugs (DMOADs), only pharmaceuticals for pain management. OA progression, particularly for post-traumatic osteoarthritis (PTOA), is associated with inflammation and enzymatic degradation of the extracellular matrix. In particular, Matrix Metalloproteinase 13 (MMP13) breaks down collagen type 2 (CII), a key structural component of cartilage extracellular matrix, and consequently, matrix degradation fragments perpetuate inflammation and a degenerative cycle that leads to progressive joint pathology. Here, we tested targeted delivery of endosome-escaping, MMP13 RNA interference (RNAi) nanoparticles (NPs) as a DMOAD. The new targeting approach pursued here deviates from the convention of targeting specific cell types (e.g., through cell surface receptors) and instead leverages a monoclonal antibody (mAbCII) that targets extracellular CII that becomes uniquely accessible at early OA focal defects. Targeted mAbCII-siNPs create an in situ NP depot for retention and potent activity within OA joints. The mAbCII-siNPs loaded with MMP13 siRNA (mAbCII-siNP/siMMP13) potently suppressed MMP13 expression (95% silencing) in TNFα-stimulated chondrocytes in vitro, and the targeted mAbCII-siNPs had higher binding to trypsin-damaged porcine cartilage than untargeted control NPs. In an acute mechanical injury mouse model of PTOA, mAbCII-siNP/siMMP13 achieved 80% reduction in MMP13 expression (p = 0.00231), whereas a non-targeted control achieved only 55% silencing. In a more severe, PTOA model, weekly mAbCII-siNP/siMMP13 long-term treatment provided significant protection of cartilage integrity (0.45+/− .3 vs 1.6+/−.5 on the OARSI scale; p=0.0166), and overall joint structure (1.3+/−.6 vs 2.8+/−.2 on the Degenerative Joint Disease scale; p<0.05). Intra-articular mAbCII-siNPs better protected articular cartilage (OARSI score) relative to either single or weekly treatment with the clinical gold stand steroid treatment methylprednisolone. Finally, multiplexed gene expression analysis of 254 inflammation-related genes showed that MMP13 inhibition suppressed clusters of genes associated with tissue restructuring, angiogenesis (associated with synovial inflammation and thickening), innate immune response, and proteolysis. This work establishes the new concept of targeting unique local extracellular matrix signatures to sustain retention and increase delivery efficacy of biologics with intracellular activity and also validates the promise of MMP13 RNAi as a DMOAD in a clinically-relevant therapeutic context. Abstract Figure:PTOA targeted delivery of MMP13 siRNA to block disease progressionThe top left schematic illustrates the progression (left to right) from healthy knee joint, through inflammation induction following traumatic injury, to cartilage loss and degenerative joint disease (including synovial response). Degradation of cartilage enhances inflammation, inducing a degenerative cycle (middle right). The bottom of the graphic illustrates the concept of the matrix targeted nanocarriers for enhanced retention and activity of MMP13 siRNA at sites of cartilage injury.

Sign in / Sign up

Export Citation Format

Share Document