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Changes in serum cartilage marker levels indicate altered cartilage metabolism in families with the osteoarthritis-related type II collagen gene COL2A1 mutation.
Arthritis Rheum. 1999 Jan; 42(1):39-45.AR

Abstract

OBJECTIVE

The Arg5l9-Cys mutation in type II collagen results in severe, precocious familial osteoarthritis (OA) in 100% of carriers within the first 3 decades of life. The carrier population provided a well-defined patient population for the study of serum markers of familial OA with respect to pathogenesis, diagnosis, and prognosis.

METHODS

Serum was obtained from 31 mutation-positive individuals and 16 mutation-negative individuals. OA severity was determined by clinical and radiologic assessments. Levels of serum cartilage oligomeric matrix protein (COMP), keratan sulfate (KS) epitope, the 846 epitope of aggrecan, and the C propeptide of type II collagen (CPII) were measured and were correlated with the radiologic findings.

RESULTS

COMP and KS levels, both of which have been suggested to be indicative of disturbed cartilage turnover, were significantly elevated in mutation-positive individuals and in the individuals with OA regardless of mutation status. There was no statistically significant difference between mutation-positive, mutation-negative, OA-positive, and OA-negative individuals with respect to serum concentrations of epitope 846 or CPII, both of which are putative markers of cartilage repair.

CONCLUSION

Study of the macromolecular constituents of cartilage released into serum in subjects with familial OA revealed altered metabolism in OA, as demonstrated by elevated COMP and KS levels. Other constituents, the 846 epitope and CPII, were not altered, indicating dissociation of cartilage anabolism and breakdown. Future sequential studies will provide an opportunity to define biochemical changes as familial OA develops and to monitor therapeutic responses.

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Authors+Show Affiliations

Bleasel JF
Case Western Reserve University, Cleveland, Ohio 44106, USA.
Poole AR
No affiliation info available
Heinegård D
No affiliation info available
Saxne T
No affiliation info available
Holderbaum D
No affiliation info available
Ionescu M
No affiliation info available
Jones P
No affiliation info available
Moskowitz RW
No affiliation info available

MeSH

AdultAgedBiomarkersCartilageCartilage Oligomeric Matrix ProteinCobaltCollagenEpitopesExtracellular Matrix ProteinsFamily HealthFemaleGlycoproteinsHumansMaleMatrilin ProteinsMiddle AgedOsteoarthritis

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

9920012

Citation

Bleasel, J F., et al. "Changes in Serum Cartilage Marker Levels Indicate Altered Cartilage Metabolism in Families With the Osteoarthritis-related Type II Collagen Gene COL2A1 Mutation." Arthritis and Rheumatism, vol. 42, no. 1, 1999, pp. 39-45.
Bleasel JF, Poole AR, Heinegård D, et al. Changes in serum cartilage marker levels indicate altered cartilage metabolism in families with the osteoarthritis-related type II collagen gene COL2A1 mutation. Arthritis Rheum. 1999;42(1):39-45.
Bleasel, J. F., Poole, A. R., Heinegård, D., Saxne, T., Holderbaum, D., Ionescu, M., Jones, P., & Moskowitz, R. W. (1999). Changes in serum cartilage marker levels indicate altered cartilage metabolism in families with the osteoarthritis-related type II collagen gene COL2A1 mutation. Arthritis and Rheumatism, 42(1), 39-45.
Bleasel JF, et al. Changes in Serum Cartilage Marker Levels Indicate Altered Cartilage Metabolism in Families With the Osteoarthritis-related Type II Collagen Gene COL2A1 Mutation. Arthritis Rheum. 1999;42(1):39-45. PubMed PMID: 9920012.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Changes in serum cartilage marker levels indicate altered cartilage metabolism in families with the osteoarthritis-related type II collagen gene COL2A1 mutation. AU - Bleasel,J F, AU - Poole,A R, AU - Heinegård,D, AU - Saxne,T, AU - Holderbaum,D, AU - Ionescu,M, AU - Jones,P, AU - Moskowitz,R W, PY - 1999/1/27/pubmed PY - 1999/1/27/medline PY - 1999/1/27/entrez SP - 39 EP - 45 JF - Arthritis and rheumatism JO - Arthritis Rheum VL - 42 IS - 1 N2 - OBJECTIVE: The Arg5l9-Cys mutation in type II collagen results in severe, precocious familial osteoarthritis (OA) in 100% of carriers within the first 3 decades of life. The carrier population provided a well-defined patient population for the study of serum markers of familial OA with respect to pathogenesis, diagnosis, and prognosis. METHODS: Serum was obtained from 31 mutation-positive individuals and 16 mutation-negative individuals. OA severity was determined by clinical and radiologic assessments. Levels of serum cartilage oligomeric matrix protein (COMP), keratan sulfate (KS) epitope, the 846 epitope of aggrecan, and the C propeptide of type II collagen (CPII) were measured and were correlated with the radiologic findings. RESULTS: COMP and KS levels, both of which have been suggested to be indicative of disturbed cartilage turnover, were significantly elevated in mutation-positive individuals and in the individuals with OA regardless of mutation status. There was no statistically significant difference between mutation-positive, mutation-negative, OA-positive, and OA-negative individuals with respect to serum concentrations of epitope 846 or CPII, both of which are putative markers of cartilage repair. CONCLUSION: Study of the macromolecular constituents of cartilage released into serum in subjects with familial OA revealed altered metabolism in OA, as demonstrated by elevated COMP and KS levels. Other constituents, the 846 epitope and CPII, were not altered, indicating dissociation of cartilage anabolism and breakdown. Future sequential studies will provide an opportunity to define biochemical changes as familial OA develops and to monitor therapeutic responses. SN - 0004-3591 UR - https://www.unboundmedicine.com/medline/citation/9920012/Changes_in_serum_cartilage_marker_levels_indicate_altered_cartilage_metabolism_in_families_with_the_osteoarthritis_related_type_II_collagen_gene_COL2A1_mutation_ L2 - https://doi.org/10.1002/1529-0131(199901)42:1<39::AID-ANR5>3.0.CO;2-Y DB - PRIME DP - Unbound Medicine ER -