Consequences of chondrocyte hypertrophy on osteoarthritic cartilage: potential effect on angiogenesis

Pesesse, Laurence; Sanchez, Christelle; Delcour, Jean-Pierre; Bellahcène, Akeila; Baudouin, C.; Msika, Philippe; Henrotin, Yves

doi:10.1016/j.joca.2013.08.018

Cited by 50 publications

(62 citation statements)

References 47 publications

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“…Our findings confirm the notion of chondrocyte phenotype modulation in OA that chondrocytes in diseased cartilage undergo terminal differentiation to hypertrophy. Moreover, some characteristics of OA such as remodeling of extracellular matrix by proteases, vascularization and focal calcification of joint resemble the physiological differentiation process of chondrocyte during skeletal development 4,6,7,12,27 .…”

Section: Discussionmentioning

confidence: 99%

Potential diagnostic value of a type X collagen neo-epitope biomarker for knee osteoarthritis

Manon‐Jensen

Arendt-Nielsen

et al. 2019

Osteoarthritis and Cartilage

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s u m m a r yObjective: Phenotypic changes of chondrocytes toward hypertrophy might be fundamental in the pathogenesis of osteoarthritis (OA), of which type X collagen (Col10) is a well-known marker. The purpose was to develop a specific immunoassay for blood quantification of a newly identified neo-epitope of type Col10 to assess its diagnostic value for radiographic knee OA. Methods: A neo-epitope of Col10 was identified in urine samples from OA patients. A monoclonal antibody against the neo-epitope was produced in Balb/C mice. The enzyme responsible for the cleavage was identified. Immunohistochemical detection of this neo-epitope was performed on human OA cartilage. An immunoassay (Col10neo) was developed and quantified in two clinical studies: the C4Pain-003 and the NYU OA progression study. Receiver operating characteristic curve (ROC) curve analysis was carried out to evaluate the discriminative power of Col10neo between OA and rheumatoid arthritis (RA). Results: A neo-epitope specific mAb was produced. The Cathepsin K-generated neo-epitope was localized to the pericellular matrix of chondrocytes, while its presence was extended and more prominent in superficial fibrillation in the cartilage with advanced degradation. In the C4Pain study, a higher level of Col10neo was seen in subjects with greater KL grade. The group of the highest tertile of Col10neo included more subjects with KL3-4. In the NYU study, Col10neo was statistically higher in OA than control or RA. ROC curve analysis revealed area under the curve was 0.88 (95% CI 0.81e0.94). Conclusion: Our findings indicate that Col10neo linked to hypertrophic chondrocytes could be used as a diagnostic biochemical marker for knee OA.

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Section: Discussionmentioning

confidence: 99%

Potential diagnostic value of a type X collagen neo-epitope biomarker for knee osteoarthritis

Manon‐Jensen

Arendt-Nielsen

et al. 2019

Osteoarthritis and Cartilage

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“…In healthy cartilage, the flow of fluid enables nutrients and oxygen to diffuse in the tissue, and the deep calcified cartilage layer functions as a physical barrier for diffusion and angiogenesis (i.e., invasion of blood vessels) between cartilage and subchondral bone . However, in diseased OA cartilage, fluid permeability increases as a result of angiogenesis in the deep calcified cartilage and contributes to deleterious changes in cartilage mechanical properties . Higher T2 values in the deep cartilage layer are possibly related to increased hydraulic permeability in the cartilage‐subchondral bone unit, which has been associated with OA progression.…”

Section: Discussionmentioning

confidence: 99%

Cartilage quantitative T2 relaxation time 2–4 years following isolated anterior cruciate ligament reconstruction

Wang

Wrigley

Bennell

et al. 2018

Journal Orthopaedic Research

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Cartilage T2 relaxation time in isolated anterior cruciate ligament reconstruction (ACLR) without concomitant meniscal pathology and their changes over time remain unclear. The purpose of this exploratory study was to: (i) compare cartilage T2 relaxation time (T2 values) in people with isolated ACLR at 2-3 years post-surgery (baseline) and matched healthy controls and; (ii) evaluate the subsequent 2-year change in T2 values in people with ACLR. Twenty-eight participants with isolated ACLR and nine healthy volunteers underwent knee magnetic resonance imaging (MRI) at baseline; 16 ACLR participants were re-imaged 2 years later. Cartilage T2 values in full thickness, superficial layers, and deep layers were quantified in the tibia, femur, trochlear, and patella. Between-group comparisons at baseline were performed using analysis of covariance adjusting for age, sex, and body mass index. Changes over time in the ACLR group were evaluated using paired sample t-tests. ACLR participants showed significantly higher (p = 0.03) T2 values in the deep layer of medial femoral condyle at baseline compared to controls (mean difference 4.4 ms [13%], 95%CI 0.4, 8.3 ms). Over 2 years, ACLR participants showed a significant reduction (p = 0.04) in T2 value in the deep layer of lateral tibia (mean change 1.4 ms [-7%], 95%CI 0.04, 2.8 ms). The decrease in T2 values suggests improvement in cartilage composition in the lateral tibia (deep layer) of ACLR participants. Further research with larger ACLR cohorts divided according to meniscal status and matched healthy cohorts are needed to further understand cartilage changes post-ACLR. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:2022-2029, 2018.

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“…Cartilage in joints and endplate cartilage in the spine are normally avascular. During OA development, angiogenesis may occur from blood vessels in the subchondral bone to the cartilage, but also in the inflamed synovium and osteophytes [43][44][45]. Therefore, 18 F-FPRGD 2 uptake by joints and surrounding structures may be explained by the radiopharmaceutical binding to the integrin a v b 3 of activated endothelial cells thus imaging local angiogenesis [9].…”

Section: Discussionmentioning

confidence: 99%

18F-FPRGD2 PET/CT imaging of musculoskeletal disorders

et al. 2015

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Consequences of chondrocyte hypertrophy on osteoarthritic cartilage: potential effect on angiogenesis

Abstract: Hypertrophic differentiation of chondrocyte may promote angiogenesis. Our findings established the relation of BSP with OA chondrocyte hypertrophy and suggested that this factor could constitute a potential target to control cartilage neovascularisation in OA.

Cited by 50 publications

References 47 publications

Potential diagnostic value of a type X collagen neo-epitope biomarker for knee osteoarthritis

Potential diagnostic value of a type X collagen neo-epitope biomarker for knee osteoarthritis

Cartilage quantitative T2 relaxation time 2–4 years following isolated anterior cruciate ligament reconstruction

18F-FPRGD2 PET/CT imaging of musculoskeletal disorders

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