scholarly journals Ability of a Urine Assay of Type II Collagen Cleavage by Collagenases to Detect Early Onset and Progression of Articular Cartilage Degeneration: Results from a Population-based Cohort Study

2016 ◽  
Vol 43 (10) ◽  
pp. 1864-1870 ◽  
Author(s):  
A. Robin Poole ◽  
Nhuan Ha ◽  
Suzanne Bourdon ◽  
Eric C. Sayre ◽  
Ali Guermazi ◽  
...  
Keyword(s):  
Articular Cartilage ◽  
Competitive Inhibition ◽  
Cartilage Damage ◽  
Type Ii Collagen ◽  
Cartilage Degeneration ◽  
Population Based ◽  
Sandwich Assay ◽  
Radiographic Osteoarthritis ◽  
Collagen Peptide ◽  
Increased Risk

Objective.To evaluate the association of a sandwich assay for cartilage collagenase-mediated degradation, the C2C human urine sandwich assay (IB-C2C-HUSA), with early and late knee cartilage pathology and with progression of cartilage damage.Methods.A population-based cohort with knee pain, age 40–79 years, was evaluated at baseline (n = 253) and after mean 3.3 years (n = 161). We evaluated the IB-C2C-HUSA and a related competitive inhibition assay (C2C). The C2C assay was applied to serum (sC2C) and urine (uC2C). Based on knee radiographs and magnetic resonance imaging (MRI), 3 subgroups [no cartilage pathology, preradiographic cartilage pathology, and radiographic osteoarthritis (ROA)] were evaluated cross-sectionally for association with biomarker levels. Longitudinally, we evaluated whether baseline assays predict subsequent progression of cartilage degeneration, defined by MRI cartilage loss.Results.Cross-sectionally, statistically significant differences were seen in the 3 subgroups for IB-C2C-HUSA (p < 0.001), with the highest levels seen in ROA, and for sC2C (p = 0.023), while no differences were seen for uC2C (p = 0.501). Baseline IB-C2C-HUSA levels were higher in progressors vs nonprogressors (p = 0.003). In logistic regression analysis, only baseline IB-C2C-HUSA was associated with an increased risk of progression of cartilage damage (OR 1.78, 95% CI 1.03–3.09).Conclusion.The IB-C2C-HUSA degradation assay detects the generation of a pathology-related cartilage collagen peptide(s) that increase(s) with onset of degeneration of knee articular cartilage. The baseline values are associated with progression of cartilage degeneration over 3 subsequent years. This assay may have value in clinical OA trials. Further, it points to collagenase activity as a therapeutic target for controlling degeneration of articular cartilage.

scholarly journals Presence of MRI-detected joint effusion and synovitis increases the risk of cartilage loss in knees without osteoarthritis at 30-month follow-up: the MOST study

2011 ◽  
Vol 70 (10) ◽  
pp. 1804-1809 ◽  
Author(s):  
Frank W Roemer ◽  
Ali Guermazi ◽  
David T Felson ◽  
Jingbo Niu ◽  
Michael C Nevitt ◽  
...  
Keyword(s):  
Cartilage Damage ◽  
Multivariable Analysis ◽  
Cartilage Loss ◽  
Joint Effusion ◽  
Proton Density ◽  
Osteoarthritis Of The Knee ◽  
Radiographic Osteoarthritis ◽  
Baseline Visit ◽  
Increased Risk

ObjectiveTo evaluate if two different measures of synovial activation, baseline Hoffa synovitis and effusion synovitis, assessed by MRI, predict cartilage loss in the tibiofemoral joint at 30 months follow-up in subjects with neither cartilage damage nor tibiofemoral radiographic osteoarthritis of the knee.MethodsNon-contrast-enhanced MRI was performed using proton density-weighted fat-suppressed sequences in the axial and sagittal planes and a short tau inversion recovery sequence in the coronal plane. Hoffa synovitis, effusion synovitis and cartilage status were assessed semiquantitatively according to the WORMS scoring system. Included were knees that had neither radiographic osteoarthritis nor MRI-detected tibiofemoral cartilage damage at the baseline visit. The presence of Hoffa synovitis was defined as any grade ≥2 (range 0–3) and effusion synovitis as any grade ≥2 (range 0–3). Logistic regression was performed to examine the relation of the presence of either measure to the risk of cartilage loss at 30 months adjusting for other potential confounders.ResultsOf 514 knees included in the analysis, the prevalence of Hoffa synovitis and effusion synovitis at the baseline visit was 8.4% and 10.3%, respectively. In the multivariable analysis, baseline effusion synovitis was associated with an increased risk of cartilage loss. No such association was observed for baseline Hoffa synovitis.ConclusionsBaseline effusion synovitis, but not Hoffa synovitis, predicted cartilage loss. The findings suggest that effusion synovitis, a reflection of inflammatory activity including joint effusion and synovitic thickening, may play a role in the future development of cartilage lesions in knees without osteoarthritis.

Type II Collagen Peptide Release from Rabbit Articular Cartilage

1999 ◽  
Vol 878 (1 INHIBITION OF) ◽  
pp. 590-593 ◽  
Author(s):  
B. R. FELICE ◽  
C. O. CHICHESTER ◽  
H.-J. BARRACH
Keyword(s):  
Articular Cartilage ◽  
Type Ii Collagen ◽  
Type Ii ◽  
Collagen Peptide ◽  
Peptide Release ◽  
Rabbit Articular Cartilage

scholarly journals HDAC4 mutant represses chondrocyte hypertrophy by locating in the nucleus and attenuates disease progression of posttraumatic osteoarthritis

2022 ◽  
Vol 23 (1) ◽  
Author(s):  
Xiaodong Gu ◽  
Fei Li ◽  
Yangyang Gao ◽  
Xianda Che ◽  
Pengcui Li
Keyword(s):  
Articular Cartilage ◽  
Histone Deacetylase ◽  
Cartilage Damage ◽  
Adenovirus Vector ◽  
Cartilage Degeneration ◽  
Sprague Dawley ◽  
Chondrocyte Hypertrophy ◽  
Sprague Dawley Rats ◽  
Histone Deacetylase 4 ◽  
Safranin O

Abstract Background The aim of this study was to evaluate whether histone deacetylase 4 S246/467/632A mutant (m-HDAC4) has enhanced function at histone deacetylase 4 (HDAC4) to attenuate cartilage degeneration in a rat model of osteoarthritis (OA). Methods Chondrocytes were infected with Ad-m-HDAC4-GFP or Ad-HDAC4-GFP for 24 h, incubated with interleukin-1β (IL-1β 10 ng/mL) for 24 h, and then measured by RT-qPCR. Male Sprague-Dawley rats (n = 48) were randomly divided into four groups and transduced with different vectors: ACLT/Ad-GFP, ACLT/Ad-HDAC4-GFP, ACLT/Ad-m-HDAC4-GFP, and sham/Ad-GFP. All rats received intra-articular injections 48 h after the operation and every 3 weeks thereafter. Cartilage damage was assessed using radiography and Safranin O staining and quantified using the OARSI score. The hypertrophic and anabolic molecules were detected by immunohistochemistry and RT-qPCR. Results M-HDAC4 decreased the expression levels of Runx-2, Mmp-13, and Col 10a1, but increased the levels of Col 2a1 and ACAN more effectively than HDAC4 in the IL-1β-induced chondrocyte OA model; upregulation of HDAC4 and m-HDAC4 in the rat OA model suppressed Runx-2 and MMP-13 production, and enhanced Col 2a1 and ACAN synthesis. Stronger Safranin O staining was detected in rats treated with m-HDAC4 than in those treated with HDAC4. The resulting OARSI scores were lower in the Ad-m-HDAC4 group (5.80 ± 0.45) than in the Ad-HDAC4 group (9.67 ± 1.83, P = 0.045). The OARSI scores were highest in rat knees that underwent ACLT treated with Ad-GFP control adenovirus vector (14.93 ± 2.14, P = 0.019 compared with Ad-HDAC4 group; P = 0.003 compared with Ad-m-HDAC4 group). Lower Runx-2 and MMP-13 production, and stronger Col 2a1 and ACAN synthesis were detected in rats treated with m-HDAC4 than in those treated with HDAC4. Conclusions M-HDAC4 repressed chondrocyte hypertrophy and induced chondrocyte anabolism in the nucleus. M-HDAC4 was more effective in attenuating articular cartilage damage than HDAC4.

scholarly journals Rat Chondrocyte Inflammation and Osteoarthritis Are Ameliorated by Madecassoside

2020 ◽  
Vol 2020 ◽  
pp. 1-10 ◽  
Author(s):  
Safwat Adel Abdo Moqbel ◽  
Yuzhe He ◽  
Langhai Xu ◽  
Chiyuan Ma ◽  
Jisheng Ran ◽  
...  
Keyword(s):  
Therapeutic Potential ◽  
Cartilage Damage ◽  
Centella Asiatica ◽  
Type Ii Collagen ◽  
Cartilage Degeneration ◽  
Treated Group ◽  
Joint Disease ◽  
Inflammatory Factors ◽  
Protective Effects ◽  
Osteoarthritic Chondrocytes

As a joint disease, osteoarthritis (OA) is caused by the breakdown of subchondral bone and cartilage damage. Inflammatory factors, such as interleukin- (IL-) 1β, mediate the progression of OA. Madecassoside (MA), a triterpenoid component derived from the gotu kola herb (Centella asiatica), exhibits various pharmacological effects, including antioxidative and anti-inflammatory properties. In the present study, the protective effects and possible mechanism of MA on the treatment of OA were investigated. MA was demonstrated to significantly suppress the IL-1β-induced overexpression of matrix metalloproteinase- (MMP-) 3, MMP-13, inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2) and to decrease the IL-1β-induced degradation of type II collagen and sox9. Additionally, MA was able to reduce the IL-1β-induced phosphorylation of p65 in osteoarthritic chondrocytes. Furthermore, in a rat OA model, MA prevented cartilage degeneration and reduced the OARSI score in the MA-treated group compared with the OA group. The present study showed that MA suppresses the nuclear factor-κB signaling pathway, reducing IL-1β-induced chondrocyte inflammation, which indicates the therapeutic potential of MA in patients with OA.

A NIR-II fluorescent probe for articular cartilage degeneration imaging and osteoarthritis detection

2019 ◽  
Vol 7 (3) ◽  
pp. 1043-1051 ◽  
Author(s):  
Wanrong Yi ◽  
Hui Zhou ◽  
Anguo Li ◽  
Ying Yuan ◽  
Yaqi Guo ◽  
...  
Keyword(s):  
Articular Cartilage ◽  
Fluorescent Probe ◽  
Type Ii Collagen ◽  
Cartilage Degeneration ◽  
Type Ii ◽  
Early Osteoarthritis ◽  
Collagen Binding ◽  
Binding Peptide ◽  
Articular Cartilage Degeneration

A Type II collagen-binding peptide based NIR-II fluorescent probe for articular cartilage degeneration imaging and early osteoarthritis detection.

Application of Microforming to Create Chondrocyte Home Sites in a Natural Cartilage Matrix

2014 ◽  
Author(s):  
Theodore W. Vandenberg ◽  
Christopher R. Nehme ◽  
Thomas P. James
Keyword(s):  
Articular Cartilage ◽  
Statistical Significance ◽  
Cartilage Damage ◽  
Cartilage Degeneration ◽  
Cartilage Tissue ◽  
Pathological Feature ◽  
The Matrix ◽  
Controlling Processes ◽  
Articular Cartilage Degeneration

Articular cartilage degeneration is a central pathological feature of osteoarthritis. Cartilage in the adult does not regenerate in vivo and, as a result, cartilage damage in osteoarthritis is irreversible. With our ever-aging population, osteoarthritis has become a leading cause of disability and unfortunately, no optimal treatments for osteoarthritis are currently available. To address this problem, a research community is focused on the development of both natural and synthetic biodegradable tissue scaffolds. The scaffolds must contain depressions or holes for the purpose of chondrocyte seeding and growth in order to create an implantable construct. In addition to chondrocytes, cartilage tissue consists of the extracellular matrix (ECM). Studies of many tissue types have established that ECM plays an important role in regulating cell behavior and controlling processes such as tissue differentiation and tumor progression. Unlike most natural tissues, adult cartilage ECM is exceptionally dense and lacking in vascularity, which makes it difficult for chondrocytes to be transplanted directly into the matrix. Current methods of creating cell home sites through chemical decellularization of the ECM degrade the mechanical integrity of the cartilage tissue. The research conducted here used a mechanical, rather than chemical, method to create cell home sites. A novel micropunching machine was developed to fabricate 200 μm diameter holes in cartilage, thereby creating a porous natural scaffold while maintaining a healthy ECM. Equine articular cartilage slices were harvested from the cadaver’s back knee joint and cryo-sectioned into 100 μm thick slices. Using die clearances of 3.7%, 6.8%, and 8.9%, the results indicate that micro-scale holes can be mechanically punched in cartilage tissue. The maximum punching force showed a slight trend of decreasing as die clearance increased, but there was no statistical significance. Punching force, as well as hole size, was highly dependent on sample hydration. Upon inspection, the resulting hole sizes were approximately 50 μm to 150 um, indicating 25% to 75% shrinkage in reference to the male punch diameter. Finally, the resulting hole shape was observed to be slightly non-circular and the edges of the hole exhibited a raggedness, which was indicative of the cartilage tearing during hole punching.

scholarly journals Development of Tissue-Engineered Human Articular Cartilage

2000 ◽  
Author(s):  
Mark A. Applegate
Keyword(s):  
Articular Cartilage ◽  
Sports Injuries ◽  
Cartilage Damage ◽  
Fibrous Tissue ◽  
Cartilage Degeneration ◽  
Cartilage Defects ◽  
Human Articular Cartilage ◽  
Total Knee Replacements ◽  
Alternative Procedures ◽  
And Function

Abstract Disability due to joint pain is increasing as our society ages. This pain often results from cartilage degeneration in joints due to osteoarthritis or trauma. Cartilage damage from sports injuries is common and the normal repair response results in the formation of fibrous tissue that is inferior to normal cartilage in structure and function and eventually degenerates with time. As a result, tens of thousands of total knee replacements and other surgical procedures are performed each year to repair cartilage defects in the knee. A common clinical treatment for cartilage lesions is debridement of the damaged tissue followed by drilling into the subchondral bone to stimulate tissue regeneration. Although this procedure often provides pain relief, it does not restore long-term function and frequently hastens additional degeneration of the injured site. Alternative procedures for repair or regeneration of human articular cartilage are needed.

scholarly journals Hyaluronic Acid versus Alpha-2-Macroglobulin Intra-Articular Injections for Amelioration of Knee Posttraumatic Osteoarthritis: A Rat Model

2020 ◽  
Author(s):  
Shaowei Wang ◽  
Mengbo Zhu ◽  
Yanjing Guo ◽  
Ruijia Yang ◽  
Yaqiong Chang ◽  
...  
Keyword(s):  
Hyaluronic Acid ◽  
Articular Cartilage ◽  
Synovial Fluid ◽  
Rat Model ◽  
Cruciate Ligament ◽  
Cartilage Damage ◽  
Cartilage Degeneration ◽  
Protective Effects ◽  
Significant Difference ◽  
Histological Staining

Abstract Background: The study was performed to evaluate whether intra-articular injection of A2M has better effect than current commonly used Hyaluronic Acid (HA) injection therapy to attenuate cartilage degeneration in a rat anterior cruciate ligament transection (ACLT) osteoarthritis (OA) model.Method: In vivo effects of A2M and HA on cartilage degeneration were evaluated in rat surgery induced ACLT OA models. 100 rats were randomly divided into four groups: (a) Sham surgery + saline (Sham + S), (b) ACLT + A2M, (c) ACLT+HA, or (d) ACLT + saline (ACLT+S). The animals were sacrificed at 12 weeks after surgery. Histological staining was performed to assess cartilage damage. The concentration of MMP-13 and sGAG in synovial fluid lavages was measured using ELISA and spectrophotometric quantitative determination. OA-related gene expression was quantified by qPCR.Result: Indian ink staining showed that articular cartilage surface treated by A2M was relatively intact compared with the animals treated by ACLT with saline or HA injection. Histological staining indicated that early supplemental intra-articular injection of A2M attenuated OA pathogenesis in the rat ACLT model compared with the animals treated with saline and HA. However, supplemental intra-articular injection of HA showed no significant effect on cartilage protection for post traumatic OA compared with saline treatment. Elisa results showed A2M reduced the concentration of MMP-13 in synovial fluid compared with HA treatment group and other groups. RT-qPCR indicated that supplemental intra-articular A2M inhibits catabolism and enhances anabolic metabolism, while there was no significant difference in the expression of OA-related genes between ACLT+HA group and ACLT+S group. Conclusion: In rat model, intra-articular injection of A2M had obvious protective effects on cartilage degeneration compared with HA treatment. Major indexes of joint degeneration decreased, providing strong evidence for its intra-articular inhibitory effect. Meanwhile, we found no significant alleviation of articular cartilage pathogenesis in HA treated group, which suggests that the efficacy of HA is questionable and possibly transient, although it is extensively used to improve syndromes.

scholarly journals The role of accelerated growth plate fusion in the absence of SOCS2 on osteoarthritis vulnerability

2021 ◽  
Author(s):  
Hasmik Jasmine Samvelyan ◽  
Carmen Huesa ◽  
Lucy Cui Lin ◽  
Colin Farquharson ◽  
Katherine Ann Staines
Keyword(s):  
Articular Cartilage ◽  
Growth Plate ◽  
Bone Growth ◽  
Cartilage Damage ◽  
Cartilage Lesion ◽  
Cartilage Degeneration ◽  
Negative Regulator ◽  
Micro Ct ◽  
Severity Scores ◽  
Accelerated Growth

Osteoarthritis is the most prevalent systemic musculoskeletal disorder characterised by articular cartilage degeneration and subchondral bone (SCB) sclerosis. Here we sought to examine the contribution of accelerated growth to osteoarthritis development using a murine model of excessive longitudinal growth. Suppressor of cytokine signalling 2 (SOCS2) is a negative regulator of growth hormone (GH) signalling, thus mice deficient in SOCS2 (Socs2-/-) display accelerated bone growth. We examined vulnerability of Socs2-/- mice to osteoarthritis following surgical induction of disease (destabilisation of the medial meniscus (DMM)), and with ageing, by histology and micro-CT. We observed significant increase in number (WT DMM: 532± 56; WT sham: 495± 45; KO DMM: 169± 49; KO sham: 187± 56; P<0.01) and density (WT DMM: 2.2± 0.9; WT sham: 1.2± 0.5; KO DMM: 13.0± 0.5; KO sham: 14.4± 0.7) of growth plate bridges in Socs2-/- in comparison to wild-type (WT). Histological examination of WT and Socs2-/- knees revealed articular cartilage damage with DMM in comparison to sham (WT DMM: 3.4± 0.4; WT sham: 0.3± 0.05 (P<0.05); KO DMM: 3.2± 0.8; KO sham: 0.8± 0.3). Articular cartilage lesion severity scores (mean and maximum) were similar in WT and Socs2-/- mice with either DMM, or with ageing. Micro-CT analysis revealed significant decreases in SCB thickness, epiphyseal trabecular number and thickness in the medial compartment of Socs2-/-, in comparison to WT (P<0.001). DMM had no effect on the SCB thickness in comparison to sham in either genotype. Together these data suggest that enhanced GH signalling through SOCS2 deletion accelerates growth plate fusion, however this has no effect on osteoarthritis vulnerability in this model.

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