A New Biochemical Marker for Joint Injury. Analysis of Ykl-40 in Serum and Synovial Fluid

Johansen, Julia S.; Jensen, Hanne; Price, Paul A.

doi:10.1093/rheumatology/32.11.949

Cited by 205 publications

(109 citation statements)

References 0 publications

Supporting

Mentioning

103

Contrasting

Unclassified

Order By: Relevance

“…The presence of HC gp-39 in the inflamed joints of RA patients had already been demonstrated in previous investigations (13,34) and was confirmed in the present study, in which we observed high levels of HC gp-39 in the SF of all RA patients tested (10-15 fold higher than published serum levels [11][12][13]). In addition, we demonstrated the presence of MIA in both SF (ϳ3-fold higher than in serum [data not shown]) and in ST of RA patients.…”

Section: Discussionsupporting

confidence: 92%

“…Although the physiologic function of HC gp-39 is still unknown, its expression is specifically induced under pathologic conditions such as RA (8,(11)(12)(13). In RA patients, HC gp-39 is expressed not only by chondrocytes, but also by mature CD16-positive macrophages in the synovium (14) and by peripheral blood-derived macrophages during their differentiation from monocytes (15)(16)(17)(18).…”

mentioning

confidence: 99%

See 1 more Smart Citation

Endogenous HLA–DR–restricted presentation of the cartilage antigens human cartilage gp‐39 and melanoma inhibitory activity in the inflamed rheumatoid joint

Lierop¹,

Hoed²,

Houbiers³

et al. 2007

Arthritis & Rheumatism

View full text Add to dashboard Cite

Objective. The cartilage proteins melanoma inhibitory activity (MIA) and human cartilage gp-39 (HC gp-39) are candidate autoantigens in rheumatoid arthritis (RA). The present study was undertaken to investigate the endogenous HLA-DR4-restricted presentation of these self proteins, in order to seek in vivo evidence in support of their potential immunologic role. The mechanisms that cause and sustain rheumatoid arthritis (RA) remain poorly elucidated. The association of the disease with certain class II major histocompatibility complex (MHC) haplotypes, however, strongly suggests that specific antigens are presented by antigen-presenting cells (APCs) to CD4ϩ T lymphocytes (1,2). Previous studies indicate that cartilage could be the source of some of these antigens in RA (3-7). In the present study we investigated the local presence and presentation of 2 cartilage-derived proteins that have distinct properties: human cartilage gp-39 (HC gp-39) and a protein called melanoma inhibitory activity (MIA).

show abstract

Section: Discussionsupporting

confidence: 92%

mentioning

confidence: 99%

Endogenous HLA–DR–restricted presentation of the cartilage antigens human cartilage gp‐39 and melanoma inhibitory activity in the inflamed rheumatoid joint

Lierop¹,

Hoed²,

Houbiers³

et al. 2007

Arthritis & Rheumatism

View full text Add to dashboard Cite

show abstract

“…Fraction 79 gave a band 2 at 40 kDa upon SDS-PAGE ( Fig. 1, inset) and proved to be YKL-40 by the criteria of N-terminal protein sequencing (YKLVXYYTSW-) and by radioimmunoassay (9). The next most abundant protein component in chondrocyte-conditioned medium emerges in an asymmetric peak centered at fraction 70.…”

Section: Resultsmentioning

confidence: 96%

“…YKL-40 was subsequently discovered as a heparin-binding protein in the conditioned medium of human synoviocytes (8), chondrocytes (4,9), and the MG-63 osteosarcoma cell line (10). YKL-40 has also been discovered as a heparin-binding protein expressed by porcine vascular smooth muscle cells undergoing a differentiation transition (11) and as a protein expressed selectively by murine mammary tumors initiated by neu/ras oncogenes (12).…”

mentioning

confidence: 99%

Isolation and Sequence of a Novel Human Chondrocyte Protein Related to Mammalian Members of the Chitinase Protein Family

Trinh

Figueira

et al. 1996

Journal of Biological Chemistry

185

137

View full text Add to dashboard Cite

We describe the isolation of a novel protein from the conditioned medium of human articular cartilage chondrocytes in primary culture. This 39-kDa protein has the N-terminal sequence YKL, which we have termed YKL-39. The 1434-nucleotide sequence of the YKL-39 cDNA predicts a 385-residue initial translation product and a 364-residue mature YKL-39. The amino acid sequence of YKL-39 is most closely related to YKL-40, followed by macrophage chitotriosidase, oviductal glycoprotein, and macrophage YM-1. All five proteins share significant sequence identity with bacterial chitinases and have the probable structure of an (␣␤) 8 barrel. YKL-39 lacks the active site glutamate, which is essential for the activity of chitinases, and as expected has no chitinase activity. The highest level of YKL-39 mRNA expression is seen in chondrocytes, followed by synoviocytes, lung, and heart. YKL-39 accounts for 4% of the protein in chondrocyte-conditioned medium, prostromelysin accounts for 17%, and YKL-40 accounts for 33%. In contrast to YKL-40, YKL-39 is not a glycoprotein and does not bind to heparin.In this study we report the discovery of a new member of the mammalian protein family related in sequence to bacterial chitinases. This protein family has an (␣␤) 8 barrel structure (1, 2) and includes a protein secreted from human macrophages that does have chitinase activity, which is termed chitotriosidase (3), and three proteins with no presently known enzymatic activity, YKL-40 (4), YM-1 (GenBank TM /EBI accession number M94584), and oviductal glycoprotein (6). Because the new member of this family, which we have termed YKL-39, is more closely related in size and sequence to YKL-40 than to other members of this family, it is useful to summarize research on YKL-40 as a background for the present investigation.YKL-40 is a 40-kDa glycoprotein that was first discovered as a heparin-binding protein secreted from bovine breast tissue during the massive tissue involution that follows the cessation of lactation (7). YKL-40 was subsequently discovered as a heparin-binding protein in the conditioned medium of human synoviocytes (8), chondrocytes (4, 9), and the MG-63 osteosarcoma cell line (10). YKL-40 has also been discovered as a heparin-binding protein expressed by porcine vascular smooth muscle cells undergoing a differentiation transition (11) and as a protein expressed selectively by murine mammary tumors initiated by neu/ras oncogenes (12). The present studies were initiated to further examine the expression of YKL-40 by human articular cartilage chondrocytes in culture. In the course of these studies YKL-39 was found as a protein that copurified with YKL-40.We report here the discovery, purification, characterization, and sequence of human YKL-39. MATERIALS AND METHODSIsolation and Culture of Chondrocytes and Synoviocytes-Chondrocytes and synoviocytes were obtained from Martin Lotz, director of the University of California, San Diego osteoarthritis cell culture facility and were isolated and cultured essentially as described (13). C...

show abstract

“…In contrast to chitotriosidase, a related active chitinase that is also expressed during late stages of macrophage differentiation (19), HC-gp39 lacks hydrolytic activity, probably because of a single amino acid substitution in the catalytic center region and acts as a chitin-specific lectin (20). In vivo, HC-gp39 levels are increased in serum, synovial fluid, and cartilage of rheumatoid arthritis patients (18,21), in various inflammatory disorders (22), in the liver of patients with alcoholic cirrhosis (23), in serum of patients with recurrent breast cancer (24) and colorectal cancer (25), and in macrophages in the atherosclerotic plaque (26). The described expression pattern suggests a putative role in inflammation, tissue remodeling, and tumor metastasis.…”

mentioning

confidence: 99%

Transcriptional Regulation of CHI3L1, a Marker Gene for Late Stages of Macrophage Differentiation

Rehli

Niller

Ammon

et al. 2003

Journal of Biological Chemistry

224

179

View full text Add to dashboard Cite

The protein product of the CHI3L1 gene, human cartilage 39-kDa glycoprotein (HC-gp39), is a tissue-restricted, chitin-binding lectin and member of glycosyl hydrolase family 18. In contrast to many other monocyte/macrophage markers, its expression is absent in monocytes and strongly induced during late stages of human macrophage differentiation. To gain insights into the molecular mechanisms underlying its cell typerestricted and maturation-associated expression in macrophages, we initiated a detailed study of the proximal HC-gp39 promoter. Deletion analysis of reporter constructs in macrophage-like THP-1 cells localized a region directing high levels of macrophage-specific reporter gene expression to ϳ300 bp adjacent to the major transcriptional start site. The promoter sequence contained consensus binding sites for several known factors, and specific binding of nuclear PU.1, Sp1, Sp3, USF, AML-1, and C/EBP proteins was detectable in gel shift assays. In vivo footprinting assays with dimethyl sulfate demonstrate that the protection of corresponding sequences was enhanced in macrophages compared with monocytes. Mutational analysis of transcription factor binding sites indicated a predominant role for a single Sp1 binding site in regulating HC-gp39 promoter activity. In addition, gel shift assays using nuclear extracts of monocytes and macrophages demonstrated that the binding of nuclear Sp1, but not Sp3, markedly increases during macrophage differentiation. Our results further highlight the important role of Sp1 in macrophage gene regulation.

show abstract

A New Biochemical Marker for Joint Injury. Analysis of Ykl-40 in Serum and Synovial Fluid

Cited by 205 publications

References 0 publications

Endogenous HLA–DR–restricted presentation of the cartilage antigens human cartilage gp‐39 and melanoma inhibitory activity in the inflamed rheumatoid joint

Endogenous HLA–DR–restricted presentation of the cartilage antigens human cartilage gp‐39 and melanoma inhibitory activity in the inflamed rheumatoid joint

Isolation and Sequence of a Novel Human Chondrocyte Protein Related to Mammalian Members of the Chitinase Protein Family

Transcriptional Regulation of CHI3L1, a Marker Gene for Late Stages of Macrophage Differentiation

Contact Info

Product

Resources

About