Session Information
Session Type: Abstract Submissions (ACR)
Background/Purpose:
Osteoarthritis (OA) is the most common degenerative joint disease, of which the pathogenesis is inadequately understood. The hypertrophy-like changes, such as expression of hypertrophy markers and matrix calcification have been observed in the initiation and progression of OA. The aim of this study was to investigate the relationships of chondrocyte hypertrophy, cartilage degradation and systemic inflammation by measuring 3 biomarkers in serum of 283 OA patients.
Methods:
i) A competitive ELISA, C-Col10, was developed as a marker of chondrocyte hypertrophy, through measurement of type X collagen (ColX). ii) C-Col10, C2M (matrix metalloproteinase-derived fragments of type II collagen) and hsCRP were quantified by ELISA in serum of the patients, stratified by Kellgren-Lawrence (KL) score 0-4. iii) Association between serum levels of the 3 biomarkers were analyzed (Pearson correlations were done on log transformed data). The data is shown as mean [95%-CI]. iv) Full-depth cartilage biopsies from OA patients with different disease stages were immunostained with the C-Col10 and C2M antibodies.
Results:
The C-Col10 assay was specific for the C-terminal of type X collagen. The measurement range of the C-Col10 assay was 22-500pg/ml, with intra- and inter-assay CVs of 4.2% and 13%. There was a trend towards increasing C-Col10 levels with increasing KL score: KL0 52[24-80] pg/ml, (n=10); KL1 67 [56-78] pg/ml, (n=59); KL2 87[74-99] pg/ml, (n=144); KL3 80pg/ml [60-101], (n=36), and KL87 [47-127] pg/ml, (n=22). There was significant correlation of levels between C-Col10 and hsCRP (r=0.23, P<0.0001), and C2M (r=0.55, P <0.0001). There was no correlation between C2M and hsCRP. Age and BMI adjustment didn’t change the significant correlations. OA patients with above normal hsCRP (>5) levels showed increased C-Col10, however this was independent from cartilage degradation. These data was supported by immunoloclization of C-Col10 and C2M in the OA cartilage biopsies, which showed distinct staining patterns: C-Col10 was observed in the deep zone around the pre-hypertrophic chondrocytes in mild OA, and around chondrocyte clusters in severe OA. Whereas C2M was consistently observed in all layers of the OA cartilage.
Conclusion:
Elevated C-Col10 levels were measured in OA patients and significantly higher in patients with above normal hsCRP levels, suggesting that inflammation is associated with chondrocyte hypertrophy. Correlation between C-Col10 and cartilage degradation indicated that chondrocyte hypertrophy may be involved in the cartilage degradation. All data show that chondrocyte hypertrophy is an essential step in the pathogenesis of OA and C-Col10 measurement can provide the critical information of OA disease status.
Disclosure:
Y. He,
Nordic Bioscience,
3;
N. S. Gudman,
Nordic Bioscience,
3;
N. U. Hansen,
Nordic Bioscience ,
3;
J. Wang,
Nordic Bioscience China,
3;
D. Su,
Nordic Bioscience China,
3;
Q. Zheng,
Nordic Bioscience China,
3;
O. Simonsen,
None;
K. K. Petersen,
None;
M. Kassem,
None;
M. A. Karsdal,
Nordic Bioscience ,
3;
A. C. Bay-Jensen,
Nordic Bioscnce,
3.
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/chondrocyte-hypertrophy-measured-by-the-secretion-of-collagen-type-x-is-associated-with-cartilage-degradation-and-systemic-inflammation-in-osteoarthritis/