scholarly journals Low levels of type II collagen formation (PRO-C2) are associated with response to sprifermin: A pre-defined, exploratory biomarker analysis from the FORWARD study

2021 ◽  
Author(s):  
Anne C. Bay-Jensen ◽  
Angela A. Manginelli ◽  
Morten Karsdal ◽  
Yunyun Luo ◽  
Yi He ◽  
...  
Keyword(s):  
Type Ii Collagen ◽  
Type Ii ◽  
Collagen Formation ◽  
Biomarker Analysis ◽  
Low Levels

Immunodetection of urinary C‐terminal telopeptide fragment of type II collagen: An osteoarthritis biomarker analysis

2020 ◽  
Author(s):  
Shuwei Wang ◽  
Shanlin Su ◽  
Chunyun Yu ◽  
Subash C. B. Gopinath ◽  
Zhiquan Yang
Keyword(s):  
Type Ii Collagen ◽  
Type Ii ◽  
Biomarker Analysis

scholarly journals Thyroid hormone, insulin, and glucocorticoids are sufficient to support chondrocyte differentiation to hypertrophy: a serum-free analysis.

1992 ◽  
Vol 119 (4) ◽  
pp. 989-995 ◽  
Author(s):  
R Quarto ◽  
G Campanile ◽  
R Cancedda ◽  
B Dozin
Keyword(s):  
Collagen Synthesis ◽  
Type I Collagen ◽  
Type Ii Collagen ◽  
Hypertrophic Chondrocytes ◽  
Type I ◽  
Type Ii ◽  
Type X Collagen ◽  
Serum Free ◽  
Low Levels ◽  
Complete Cell

Chondrocytes from chicken embryo tibia can be maintained in culture as adherent cells in Coon's modified Ham's F-12 medium supplemented with 10% FCS. In this condition, they dedifferentiate, losing type II collagen expression in favor of type I collagen synthesis. Their differentiation to hypertrophy can be obtained by transferring them to suspension culture. Differentiation is evidenced by the shift from type I to type II and type IX collagen synthesis and the following predominant expression of type X collagen, all markers of specific stages of the differentiation process. To identify the factors required for differentiation, we developed a serum-free culture system where only the addition of triiodothyronine (T3; 10(-11) M), insulin (60 ng/ml), and dexamethasone (10(-9) M) to the F-12 medium was sufficient to obtain hypertrophic chondrocytes. In this hormonal context, chondrocytes display the same changes in the pattern of protein synthesis as described above. For proper and complete cell maturation, T3 and insulin concentrations cannot be modified. Insulin cannot be substituted by insulin-like growth factor-I, but dexamethasone concentration can be decreased to 10(-12) M without chondrogenesis being impaired. In the latter case, the expression of type X collagen and its mRNA are inversely proportional to dexamethasone concentration. When ascorbic acid is added to the hormone-supplemented medium, differentiating chondrocytes organize their matrix leading to a cartilage-like structure with hypertrophic chondrocytes embedded in lacunae. However, this structure does not present detectable calcification, at variance with control cultures maintained in FCS. Accordingly, in the presence of the hormone mixture, the differentiating chondrocytes have low levels of alkaline phosphatase activity. This report indicates that T3 and insulin are primary factors involved in the onset and progression of chondrogenesis, while dexamethasone supports cell viability and modulates some differentiated functions.

scholarly journals The effects of radiofrequency hyperthermia on type II collagen formation in the osteoarthritic knee

2018 ◽  
Vol 5 (3) ◽  
pp. 1
Author(s):  
Zhaohua Fu ◽  
Jiaojiao Zhao ◽  
Fei Zhang ◽  
Yongfei Wu ◽  
Qingqing Cao ◽  
...  
Keyword(s):  
Type Ii Collagen ◽  
Type Ii ◽  
Osteoarthritic Knee ◽  
Collagen Formation ◽  
Radiofrequency Hyperthermia

scholarly journals A low cartilage formation and repair endotype predicts radiographic progression of symptomatic knee osteoarthritis

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Yunyun Luo ◽  
Jonathan Samuels ◽  
Svetlana Krasnokutsky ◽  
Inger Byrjalsen ◽  
Virginia B. Kraus ◽  
...  
Keyword(s):  
Cartilage Repair ◽  
Radiographic Progression ◽  
Type Ii Collagen ◽  
Joint Space ◽  
Phase Iii ◽  
Type Ii ◽  
Collagen Formation ◽  
Cartilage Formation ◽  
Symptomatic Knee Osteoarthritis ◽  
Symptomatic Knee

Abstract Background Osteoarthritis (OA) is a disease with multiple endotypes. A hallmark of OA is loss of cartilage; however, it is evident that the rate of cartilage loss differs among patients, which may partly be attributed to differential capacity for cartilage repair. We hypothesize that a low cartilage repair endotype exists and that such endotypes are more likely to progress radiographically. The aim of this study is to examine the associations of level of cartilage formation with OA severity and radiographic OA progression. We used the blood-based marker PRO-C2, reflecting type II collagen formation, to assess levels of cartilage formation. Materials and methods The type II collagen propeptide PRO-C2 was measured in the serum/plasma of knee OA subjects from New York University (NYU, n = 106) and a subcohort of the phase III oral salmon calcitonin (sCT) trial SMC021-2301 (SMC, n = 147). Risk of radiographic medial joint space narrowing (JSN) over 24 months was compared between quartiles (very low, low, moderate, and high) of PRO-C2. Associations were adjusted for age, gender, BMI, race, baseline pain levels, and baseline joint space width. Results In both the NYU and SMC cohorts, subjects with low PRO-C2 levels had greater JSN compared with subjects with high PRO-C2. Mean difference in JSN between subjects with very low and high levels of PRO-C2 was 0.65 mm (p = 0.002), corresponding to a 3.4 (1.4–8.6)-fold higher risk of progression. There was no significant effect of sCT treatment, compared with placebo, on JSN over 2 years before stratification based on baseline PRO-C2. However, there were proportionately fewer progressors in the sCT arm of the very low/low PRO-C2 group compared with the moderate/high group (Chi squared = 6.5, p = 0.011). Conclusion Serum/plasma level of type II collagen formation, PRO-C2, may be an objective indicator of a low cartilage repair endotype, displaying radiographic progression and superior response to a proanabolic drug. Level of evidence Level III post hoc exploratory analysis of one longitudinal cohort and a sub-study from one phase III clinical trial.

scholarly journals A low cartilage formation and repair endotype predicts radiographic progression of symptomatic knee osteoarthritis

2020 ◽  
Author(s):  
Yunyun Luo ◽  
Jonathan Samuels ◽  
Svetlana Krasnokutsky ◽  
Inger Byrjalsen ◽  
Virginia B. Kraus ◽  
...  
Keyword(s):  
Cartilage Repair ◽  
Radiographic Progression ◽  
Type Ii Collagen ◽  
Joint Space ◽  
Phase Iii ◽  
Type Ii ◽  
Collagen Formation ◽  
Cartilage Formation ◽  
Symptomatic Knee Osteoarthritis ◽  
Symptomatic Knee

Abstract Objective: Osteoarthritis (OA) is a disease with multiple endotypes. A hallmark of OA is loss of cartilage; however, it is evident that the rate of cartilage loss differs among patients, which may partly be attributed to differential capacity for cartilage repair. We hypothesize that a low cartilage repair endotype exists and that such endotypes are more likely to progress radiographically. The aim of this study was to examine the associations of level of cartilage formation with OA severity and radiographic OA progression. We used the blood-based marker PRO-C2, reflecting type II collagen formation, to assess levels of cartilage formation. Methods: The type II collagen propeptide PRO-C2 was measured in the serum/plasma of knee OA subjects from New York University (NYU, n=106) and a subcohort of the phase III oral salmon calcitonin (sCT) trial SMC021-2301 (SMC, n=147). The risk of radiographic medial joint space narrowing (JSN) over 24 months was compared between quartiles (very low, low, moderate, and high) of PRO-C2. Progression was defined as two-year JSN > 0.35 mm. Associations were adjusted for age, gender, BMI, race, baseline pain levels, and baseline joint space width.Results: In both the NYU and SMC cohorts, subjects with low PRO-C2 levels had greater JSN compared to subjects with high PRO-C2. The mean difference in JSN between subjects with very low and high levels of PRO-C2 was 0.65 mm (p = 0.002), corresponding to a 3.4 [1.4 – 8.6]-fold higher risk of progression. There was no significant effect of sCT treatment, compared to placebo, on JSN over two years before stratification based on baseline PRO-C2. However, there were proportionately fewer progressors in the sCT arm of the very low/low PRO-C2 group compared to the moderate/high group (chi-squared = 6.5, p = 0.011). Conclusions: Serum/plasma level of type II collagen formation, PRO-C2, may be an objective indicator of a low cartilage repair endotype, displaying radiographic progression and superior response to a proanabolic drug.

scholarly journals Intermittent Dynamic Compression Confers Anabolic Effects in Articular Cartilage

2021 ◽  
Vol 11 (16) ◽  
pp. 7469
Author(s):  
Amalie Engstrøm ◽  
Frederik S. Gillesberg ◽  
Solveig S. Groen ◽  
Peder Frederiksen ◽  
Anne-Christine Bay-Jensen ◽  
...  
Keyword(s):  
Articular Cartilage ◽  
Mechanical Loading ◽  
Kinase Inhibitor ◽  
Dynamic Compression ◽  
Compressive Loading ◽  
Type Ii Collagen ◽  
Cartilage Explants ◽  
Type Ii ◽  
Bovine Articular Cartilage ◽  
Collagen Formation

(1) Background: Mechanical loading is an essential part of the function and maintenance of the joint. Despite the importance of intermittent mechanical loading, this factor is rarely considered in preclinical models of cartilage, limiting their translatability. The aim of this study was to investigate the effects of intermittent dynamic compression on the extracellular matrix during long-term culture of bovine cartilage explants. (2) Methods: Bovine articular cartilage explants were cultured for 21 days and subjected to 20 min of 1 Hz cyclic compressive loading five consecutive days each week. Cartilage remodeling was investigated in the presence of IGF-1 or TGF-β1, as well as a TGF-β receptor 1 (ALK5) kinase inhibitor and assessed with biomarkers for type II collagen formation (PRO-C2) and fibronectin degradation (FBN-C). (3) Results: Compression of cartilage explants increased the release of PRO-C2 and FBN-C to the conditioned media and, furthermore, IGF-1 and compression synergistically increased PRO-C2 release. Inhibition of ALK5 blocked PRO-C2 and FBN-C release in dynamically compressed explants. (4) Conclusions: Dynamic compression of cartilage explants increases both type II collagen formation and fibronectin degradation, and IGF-1 interacts synergistically with compression, increasing the overall impact on cartilage formation. These data show that mechanical loading is important to consider in translational cartilage models.

Healing of Circular Defects in the Rabbit Medial Meniscus Can Occur Spontaneously and Is not Improved by Intra-Articular Hyaluronic Acid

1996 ◽  
Vol 09 (02) ◽  
pp. 60-5 ◽  
Author(s):  
N. Hope ◽  
P. Ghosh ◽  
S. Collier
Keyword(s):  
Hyaluronic Acid ◽  
Medial Meniscus ◽  
Chondroitin Sulphate ◽  
Rabbit Model ◽  
Type Ii Collagen ◽  
Type Ii ◽  
Keratan Sulphate ◽  
Meniscal Healing ◽  
Meniscus Healing ◽  
Made In

SummaryThe aim of this study was to determine the effects of intra-articular hyaluronic acid on meniscal healing. Circular defects, 1.0 mm in diameter, were made in the anterior third of the medial meniscus in rabbits. In one joint, 0.4 ml hyaluronic acid (Healon®) was instilled, and in the contralateral (control) joint, 0.4 ml Ringer’s saline. Four rabbits were killed after four, eight and 12 weeks and the menisci examined histologically. By eight weeks most of the lesions had healed by filling with hyaline-like cartilage. Healing was not improved by hyaluronic acid treatment. The repair tissue stained strongly with alcian blue, and the presence of type II collagen, keratan sulphate, and chondroitin sulphate was demonstrated by immunohistochemical localisation. In contrast to the circular defects, longitudinal incisions made in the medial menisci of a further six rabbits did not show any healing after 12 weeks, indicating that the shape of the lesion largely determined the potential for healing.The effect of hyaluronic acid on meniscal healing was tested in a rabbit model. With one millimeter circular lesions in the medial meniscus, healing by filling with hyalinelike cartilage was not significantly affected by the application of hyaluronic acid intra-articularly at the time of surgery, compared to saline controls, as assessed histologically four, eight and 12 weeks after the operation.

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