Objective: Compared with wild-type (WT) mice, biglycan/fibromodulin double-deficient mice develop severe knee osteoarthritis. We undertook this study to compare type II collagen catabolism in the 2 genotypes and to compare the usefulness of 3 biomarkers of collagen degradation (C2C [also known as Col2-3/4C(long mono)] as well as the peptide Coll2-1 and its nitrated form, Coll2-1NO2) for evaluating collagen catabolism in vivo.
Methods: In 15 WT mice and 15 biglycan/fibromodulin double-deficient mice, we determined serum levels of C2C at ages 66 and 141 days, and we determined serum levels of Coll2-1 and Coll2-1NO2 at ages 49, 81, 95, and 141 days. Expression of the biomarkers in knee sections was examined using immunohistochemistry.
Results: The mean concentrations of C2C and Coll2-1 were higher in biglycan/fibromodulin double-deficient mice at all time points. For C2C and Coll2-1, the ratio of the serum concentration in biglycan/fibromodulin double-deficient mice to that in WT mice (the double-deficient:WT ratio) was constant over time and was approximately 1.63 and approximately 1.15, respectively. In contrast, the double-deficient:WT ratio for Coll2-1NO2 varied and, depending on age, was >1 or <1. No significant correlation was found between the expression of the different biomarkers, except for a weak, negative correlation between Coll2-1NO2 and C2C. In both genotypes, antibodies to each biomarker labeled some fibroblasts in the tendons and menisci as well as chondrocytes above the tidemark in articular cartilage. Growth plates were unstained. For each biomarker, extracellular staining was limited to fibrocartilage areas in the tendons and menisci in all mice and was limited to some focal lesions of the cartilage in biglycan/fibromodulin double-deficient mice.
Conclusion: The different double-deficient:WT ratios observed with C2C, Coll2-1, and Coll2-1NO2 in the absence of any correlation between the expression of the 3 biomarkers indicate that these biomarkers give complementary, rather than redundant, information about in vivo type II collagen catabolism.
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Analysis of microarchitectural changes in a mouse temporomandibular joint osteoarthritis model.
Arch Oral Biol
December 2009
University of Connecticut Health Center, Department of Craniofacial Sciences, Farmington, 06030, United States.
Objective: Little is known about the natural progression of the disease process of temporomandibular joint (TMJ) osteoarthritis (OA), which affects approximately 1% of the US population. The goal of this study was to examine the early microarchitectural and molecular changes in the condylar cartilage and subchondral bone in biglycan/fibromodulin (Bgn/Fmod) double-deficient mice, which develop TMJ-OA at 6 months.
Methods: TMJs from 3-month-old (n=44) and 9-month-old (n=52) wild-type (WT n=46) and Bgn/Fmod (n=50) double-deficient mice were evaluated.
The chemical biomarkers C2C, Coll2-1, and Coll2-1NO2 provide complementary information on type II collagen catabolism in healthy and osteoarthritic mice.
Arthritis Rheum
October 2007
Nestlé Research Center, Lausanne, Switzerland.
Objective: Compared with wild-type (WT) mice, biglycan/fibromodulin double-deficient mice develop severe knee osteoarthritis. We undertook this study to compare type II collagen catabolism in the 2 genotypes and to compare the usefulness of 3 biomarkers of collagen degradation (C2C [also known as Col2-3/4C(long mono)] as well as the peptide Coll2-1 and its nitrated form, Coll2-1NO2) for evaluating collagen catabolism in vivo.
Methods: In 15 WT mice and 15 biglycan/fibromodulin double-deficient mice, we determined serum levels of C2C at ages 66 and 141 days, and we determined serum levels of Coll2-1 and Coll2-1NO2 at ages 49, 81, 95, and 141 days.
Accelerated osteoarthritis in the temporomandibular joint of biglycan/fibromodulin double-deficient mice.
Osteoarthritis Cartilage
September 2005
Molecular Biology of Bones and Teeth Unit, Craniofacial and Skeletal Diseases Branch, NIDCR, NIH, DHHS Bethesda, MD 20892, USA.
Objective: To investigate whether the absence of biglycan and fibromodulin, two proteoglycans expressed in cartilage, bone and tendon, resulted in accelerated osteoarthritis in the temporomandibular joint (TMJ).
Methods: Histological sections of TMJ from 3-, 6-, 9- and 18-month-old wild-type (WT) and biglycan/fibromodulin double-deficient (DKO) mice were compared. Immuno-stainings for biglycan, fibromodulin and proliferating cell nuclear antigen (PCNA) were performed.
Abnormal collagen fibrils in tendons of biglycan/fibromodulin-deficient mice lead to gait impairment, ectopic ossification, and osteoarthritis.
FASEB J
May 2002
Craniofacial and Skeletal Diseases Branch, NIDCR, National Institutes of Health, Bethesda, Maryland, USA.
Small leucine-rich proteoglycans (SLRPs) regulate extracellular matrix organization, a process essential in development, tissue repair, and metastasis. In vivo interactions of biglycan and fibromodulin, two SLRPs highly expressed in tendons and bones, were investigated by generating biglycan/fibromodulin double-deficient mice. Here we show that collagen fibrils in tendons from mice deficient in biglycan and/or fibromodulin are structurally and mechanically altered resulting in unstable joints.
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