scholarly journals Phospholipase A2 inhibitor–loaded micellar nanoparticles attenuate inflammation and mitigate osteoarthritis progression

2021 ◽  
Vol 7 (15) ◽  
pp. eabe6374
Author(s):  
Yulong Wei ◽  
Lesan Yan ◽  
Lijun Luo ◽  
Tao Gui ◽  
Biang Jang ◽  
...  

Treating osteoarthritis (OA) remains a major clinical challenge. Despite recent advances in drug discovery and development, no disease-modifying drug for knee OA has emerged with any notable clinical success, in part, due to the lack of valid and responsive therapeutic targets and poor drug delivery within knee joints. In this work, we show that the amount of secretory phospholipase A2 (sPLA2) enzyme increases in the articular cartilage in human and mouse OA cartilage tissues. We hypothesize that the inhibition of sPLA2 activity may be an effective treatment strategy for OA. To develop an sPLA2-responsive and nanoparticle (NP)–based interventional platform for OA management, we incorporated an sPLA2 inhibitor (sPLA2i) into the phospholipid membrane of micelles. The engineered sPLA2i-loaded micellar NPs (sPLA2i-NPs) were able to penetrate deep into the cartilage matrix, prolong retention in the joint space, and mitigate OA progression. These findings suggest that sPLA2i-NPs can be promising therapeutic agents for OA treatment.

2021 ◽  
Author(s):  
Yulong Wei ◽  
Lesan Yan ◽  
Lijun Luo ◽  
Tao Gui ◽  
Ahmad Amirshaghaghi ◽  
...  

ABSTRACTTreating osteoarthritis (OA) remains a major clinical challenge. Despite recent advances in drug discovery and development, no disease-modifying drug for knee OA has emerged with any significant clinical success, in part due to the lack of valid and responsive therapeutic targets and poor drug delivery within knee joints. In this work, we show that the amount of secretory phospholipase A2 (sPLA2) enzyme increases in articular cartilage in human and mouse OA cartilage tissues. We hypothesize that inhibition of sPLA2 activity may be an effective treatment strategy for OA. To develop a sPLA2-responsive and nanoparticle (NP)-based interventional platform for OA management, we incorporated a sPLA2 inhibitor (sPLA2i) into the phospholipid membrane of micelles. The engineered sPLA2i-loaded micellar nanoparticles (sPLA2i-NPs) were able to penetrate deep into the cartilage matrix, prolong retention in the joint space, and mitigate OA progression. These findings suggest that sPLA2i-NPs can be promising therapeutic agents for OA treatment.


2019 ◽  
Vol 57 (1) ◽  
pp. 33-37
Author(s):  
A. V. Petrov ◽  
N. V. Matveeva ◽  
A. A. Petrov

The aimof the study was to assess the relationship between the detection of hyperechogenic deposits (HD) in the hyaline cartilage of the knee joints (KJ) at ultrasonography in patients with osteoarthritis (OA), clinical manifestations and structural changes according to KJ ultrasonography and radiography.Material and methods.A prospective analysis of clinical, radiological and ultrasonographic data of 114 patients with knee OA was conducted. The patients were divided into two groups: 32 patients with HD detected in at least one of the KJ, and 82 patients without HD; 32 patients of the 1st group and 34 patients of the 2nd group were observed for 2 years. A comparative assessment of initial clinical manifestations (WOMAC index), x-ray data and ultrasonographic parameters of the subchondral bone, hyaline cartilage and the degree of synovial inflammation in the groups of patients at the beginning of the study and after 2 years was carried out. The exclusion criteria were other joint diseases; paroxysmal course of the inflammatory process in KJ; trauma and history of operations on KJ; ESR >20 mm/h, uric acid level >360 μmol/l and C-reactive protein >5 mg/l.Results and discussion.HD in hyaline cartilage was found in 28.1% of patients with knee OA. After 2 years HD remained in all patients having them at inclusion, and in 5.6% of the patients they were found for the first time. In 13 patients with HD in hyaline cartilage, synovial fluid was studied and in all cases calcium pyrophosphate crystals were identified by phase-contrast microscopy. The presence of HD in the hyaline cartilage of patients with knee OA was accompanied by more pronounced ultrasonographic signs of synovitis and was associated with a higher rate of osteophytes growth in the absence of the changes of the hyaline cartilage thickness according to the ultrasonography and the width of the joint space according to x-ray.Conclusion.The presence of HD in the hyaline cartilage of patients with knee OA according to ultrasound examination may be associated with the deposition of calcium pyrophosphate crystals and is associated with persistent synovitis and accelerated growth of osteophytes.


2021 ◽  
pp. 096452842110207
Author(s):  
Alexa P Spittler ◽  
Maryam F Afzali ◽  
Richard B Martinez ◽  
Lauren A Culver ◽  
Sarah E Leavell ◽  
...  

Objective: Faced with the frustration of chronic discomfort and restricted mobility due to osteoarthritis (OA), many individuals have turned to acupuncture for relief. However, the efficacy of acupuncture for OA is uncertain, as much of the evidence is inconclusive. The purpose of this study was to evaluate electroacupuncture (EA) in a rodent model of OA such that conclusions regarding its effectiveness for symptom or disease modification could be drawn. Methods: Ten 12-month-old male Hartley guinea pigs—which characteristically have moderate to advanced OA at this age—were randomly assigned to receive EA for knee OA (n = 5) or anesthesia only (control group, n = 5). Treatments were performed three times weekly for 3 weeks, followed by euthanasia 2 weeks later. Gait analysis and enclosure monitoring were performed weekly to evaluate changes in movement. Serum was collected for inflammatory biomarker testing. Knee joints were collected for histology and gene expression. Results: Animals receiving EA had significantly greater changes in movement parameters compared to those receiving anesthesia only. There was a tendency toward decreased serum protein concentrations of complement component 3 (C3) in the EA group compared to the control group. Structural and antioxidant gene transcripts in articular cartilage were increased by EA. There was no significant difference in total joint histology scores between groups. Conclusion: This study provides evidence that EA has a positive effect on symptom, but not disease, modification in a rodent model of OA. Further investigations into mechanistic pathways that may explain the efficacy of EA in this animal model are needed.


2009 ◽  
Vol 69 (01) ◽  
pp. 163-168 ◽  
Author(s):  
M C Nevitt ◽  
Y Zhang ◽  
M K Javaid ◽  
T Neogi ◽  
J R Curtis ◽  
...  

Objectives:Previous studies suggest that high systemic bone mineral density (BMD) is associated with incident knee osteoarthritis (OA) defined by osteophytes but not with joint space narrowing (JSN), and are inconsistent regarding BMD and progression of existing OA. The association of BMD with incident and progressive tibiofemoral OA was tested in a large prospective study of men and women aged 50–79 years with or at risk for knee OA.Methods:Baseline and 30-month weight-bearing posteroanterior and lateral knee radiographs were scored for Kellgren-Lawrence (K-L) grade, JSN and osteophytes. Incident OA was defined as the development of K-L grade ⩾2 at follow-up. All knees were classified for increases in grade of JSN and osteophytes from baseline. The association of gender-specific quartiles of baseline BMD with risk of incident and progressive OA was analysed using logistic regression, adjusting for covariates.Results:The mean (SD) age of 1754 subjects was 63.2 (7.8) years and body mass index was 29.9 (5.4) kg/m2. In knees without baseline OA, higher femoral neck and whole body BMD were associated with an increased risk of incident OA and increases in grade of JSN and osteophytes (p<0.01 for trends); adjusted odds were 2.3–2.9-fold greater in the highest compared with the lowest BMD quartiles. In knees with existing OA, progression was not significantly related to BMD.Conclusions:In knees without OA, higher systemic BMD was associated with a greater risk of the onset of JSN and K-L grade ⩾2. The role of systemic BMD in early knee OA pathogenesis warrants further investigation.


2021 ◽  
Vol 12 (10) ◽  
pp. 1-6
Author(s):  
Deeya Baboo ◽  
Prajwal Narayan ◽  
Ganesh Puttur

Ayurveda (Science of life) has explained about the pathogenesis and the treatment of various disorders, the incidence of some of which have increased in the present scenario due to altered diet habits and lifestyle. Janu Sandhigata Vata is one among the Vata Vyadhi which causes a lot of inconvenience and disability in day-to-day activities. It is compared to Osteoarthritis of knee in modern Science. In this case study, a female aged about 57 years presented in the OPD of SSCASRH, Bengaluru was diagnosed with Janu Sandhigata Vata of both the knee joints. Arohana Krama Matra Basti with Prasarini taila was planned as per Sharangadhara’s reference. There was significant improvement in the patient and was evaluated after treatment and also during follow up. There was marked relief with respect to her subjective complaints like pain, improved joint space, walking time, degree of flexion and extension & X ray. This type of Arohana Krama Matra Basti can be adopted in future for planning treatment in Janu Sandhigata Vata and also taken up in a larger group study to check for better relief, long term effect and reduced side effects. The case is further elaborated in the article


2009 ◽  
Vol 18 (1) ◽  
Author(s):  
Barbara Slatkowsky-Christensen ◽  
Margreth Grotle

Osteoarthritis (OA) is a complex process affecting many different joint areas in the body. The joints most commonly affected are the knees, hips, and hands. From a patho-physiological point of view, some features are crucial for the diagnosis, such as cartilage fibrillation and thinning, subchondral sclerosis and the presence of osteophytes. The currently most widely used definitions of OA include pathogenetic features (mechanical and biological events), morphologic features (changes in articular cartilage and subchondral bone) as well as clinical features (joint pain, stiffness, tenderness, limitation of movement, crepitus and occasionally inflammation/effusion).<br />The features that until now have been used for diagnosis and classification are based on radiographic and/or clinical descriptions. From a clinical perspective, OA is the most prevalent rheumatic joint disorder, causing pain and stiffness of the joints and for the individual impaired function and health status. For epidemiological descriptions of prevalence and incidence of OA, radiographic criteria are the most reliable and commonly used. Definitions of radiographic OA include descriptions of cartilage thinning (such as joint space narrowing), subchondral bone involvement (sclerosis) and/or the presence and grading of osteophytes. Although there are geographical variations in the occurrence of OA of different joint areas, OA is seen in all populations studied. The prevalence and incidence estimates show a vide variation, however. Still the epidemiological studies of OA are hampered by a number of factors including different definitions of the disorder, different subsets of disease, and low degree of correlation between different definitions (radiographic vs clinical). Several highly suggested risk factors have been identified for knee OA. Several of these may be important targets for intervention or prevention, such as physical activity, body mass index, nutritional constituents and quadriceps strength. There is a need for prospective studies evaluating risk factors in hip and hand OA. Although there are problems in studying OA epidemiologically, the available data have shown that OA is an extremely common and disabling disorder. Through a further development of both epidemiological and other methods of OA research, this area can continue to be exciting and rapidly developing.


2019 ◽  
Vol 71 (2) ◽  
pp. 300-307 ◽  
Author(s):  
Camille M. Parsons ◽  
Andrew Judge ◽  
Kirsten Leyland ◽  
Olivier Bruyère ◽  
Florence Petit Dop ◽  
...  

Medicina ◽  
2019 ◽  
Vol 55 (5) ◽  
pp. 150 ◽  
Author(s):  
Marek Paździor ◽  
Małgorzata Kiełczykowska ◽  
Jacek Kurzepa ◽  
Dorota Luchowska-Kocot ◽  
Joanna Kocot ◽  
...  

Background and Objective: Osteoarthritis (OA) is a disorder of the musculoskeletal system resulting in worsening of life condition. The research revealed the involvement of oxidative stress into both OA pathogenesis and the effects of therapeutic agents applied in OA cases. The activities of the most important antioxidant enzymes, namely superoxide dismutase (SOD), glutathione peroxidase (GPx), catalase (CAT) and total antioxidant status (TAS), in blood of the knee OA patients were studied, with the aim of clarifying which enzymatic antioxidants are involved into osteoarthritis (OA)-related oxidative stress and whether any compensatory effects occur. The results were additionally analyzed with regard to gender. Methods: Whole blood SOD (U/mL), plasma GPx (U/L) and CAT (U/mL) activities as well as plasma TAS (mmol/L)) in knee OA patients were investigated. Sixty-seven patients (49 females and 18 males) with primary knee OA were enrolled. The control comprised 21 subjects (10 females and 11 males) free of osteoarthritis or inflammation. Results: TAS was decreased in OA subjects (4.39 ± 0.53 vs. 4.70 ± 0.60), with this effect being more significant in OA females (4.31 ± 0.51 vs. 5.02 ± 0.54). GPx was depressed in all OA patients (518 ± 176 vs. 675 ± 149). In both genders, GPx was decreased, significantly in males (482 ± 185 vs. 715 ± 105). SOD was decreased in all OA patients (109 ± 32 vs. 127 ± 42). CAT showed no difference in all OA subjects vs. control, while in OA females it was depleted (20.2 (11.6–31.6) vs. 38.5 (27.9–46.6)) and in OA men it increased (26.9 (23.3–46.5) vs. 14.0 (7.0–18.6)). Conclusions: The obtained results suggest that in men some compensatory mechanisms towards OA-related oxidative stress occurred. Based on the obtained data, the introduction of antioxidant supplements into OA therapy could be suggested with further research concerning the choice of agents.


Cartilage ◽  
2020 ◽  
pp. 194760352094638
Author(s):  
Jana Plsikova Matejova ◽  
Timea Spakova ◽  
Denisa Harvanova ◽  
Marek Lacko ◽  
Vladimir Filip ◽  
...  

Objective Osteoarthritis (OA) commonly affects weight-bearing joints and is characterized by articular cartilage breakdown combined with osteophyte formation at the joint margins and chronic nonspecific inflammation of synovium. Understanding the profile of inflammation in a patient population is an essential starting point to predict or prevent OA progression. The aim of this study was to identify the profile of selected biomolecules in synovial fluid (SF) and investigate the correlation according to gender, age, and severity of the disease within patients from among the general knee OA population. Design In our study SF samples were aspirated from the knees of 65 OA patients (46 patients with early knee OA and 19 patients with end-stage knee OA according to the Kellgren-Lawrence grading scale). The concentration of interleukins (IL-6, IL-8), matrix metalloproteinases (MMP-1, MMP-3, MMP-13), MMPs inhibitors (TIMP-1, TIMP-2), cartilage oligomeric matrix protein (COMP), and adiponectin was analyzed using a multiplex ELISA-based approach. Conclusions Our results indicate significant linear correlation of MMP-13 and COMP concentration with age ( P < 0.05), but not with OA severity. In fact, 3 of the examined biomolecules, MMP-3 ( P < 0.01), TIMP-1 ( P < 0.01), and COMP ( P < 0.05) significantly correlate with the grade of knee OA and might be associated with OA severity.


2011 ◽  
Vol 39 (1) ◽  
pp. 161-166 ◽  
Author(s):  
IDA K. HAUGEN ◽  
SEBASTIAN COTOFANA ◽  
MARTIN ENGLUND ◽  
TORE K. KVIEN ◽  
DONATUS DREHER ◽  
...  

Objective.To evaluate whether features of radiographic hand osteoarthritis (OA) are associated with quantitative magnetic resonance imaging (MRI)-defined knee cartilage thickness, radiographic knee OA, and 1-year structural progression.Methods.A total of 765 participants in Osteoarthritis Initiative (OAI; 455 women, mean age 62.5 yrs, SD 9.4) obtained hand radiographs (at baseline), knee radiographs (baseline and Year 1), and knee MRI (baseline and Year 1). Hand radiographs were scored for presence of osteophytes and joint space narrowing (JSN). Knee radiographs were scored according to the Kellgren-Lawrence (KL) scale. Cartilage thickness in the medial and lateral femorotibial compartments was measured quantitatively from coronal FLASHwe images. We examined the cross-sectional and longitudinal associations between features of hand OA (total osteophyte and JSN scores) and knee cartilage thickness, 1-year knee cartilage thinning (above smallest detectable change), presence of knee OA (KL grade ≥ 3), and progression of knee OA (KL change ≥ 1) by linear and logistic regression. Both hand OA features were included in a multivariate model (if p ≤ 0.25) adjusted for age, sex, and body mass index (BMI).Results.Hand JSN was associated with reduced knee cartilage thickness (ß = −0.02, 95% CI −0.03, −0.01) in the medial femorotibial compartment, while hand osteophytes were associated with the presence of radiographic knee OA (OR 1.10, 95% CI 1.03–1.18; multivariate models) with both hand OA features as independent variables adjusted for age, sex, and BMI). Radiographic features of hand OA were not associated with 1-year cartilage thinning or radiographic knee OA progression.Conclusion.Our results support a systemic OA susceptibility and possibly different mechanisms for osteophyte formation and cartilage thinning.


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