The small proteoglycans decorin and biglycan in human articular cartilage of late-stage osteoarthritis

Bock, Hans; Michaeli, P.; Bode, Christa; Schultz, W.; Kresse, Hans; Herken, Rainer; Miosge, Nicolai

doi:10.1053/joca.2001.0420

Cited by 70 publications

(69 citation statements)

References 30 publications

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“…We detected Cilp1 and Cilp2 in heart and skeletal muscle. A number of matrix molecules are components of both tissues, including collagen types I, III, V, and VI (39 -43), tenascin-C, and decorin (6,21,28), thus CILP-2 may contribute to the structural organization and matrix architecture within these connective tissues.…”

Section: Discussionmentioning

confidence: 99%

Cartilage Intermediate Layer Protein 2 (CILP-2) Is Expressed in Articular and Meniscal Cartilage and Down-regulated in Experimental Osteoarthritis

Bernardo

Belluoccio

Rowley

et al. 2011

Journal of Biological Chemistry

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Using transcriptome profiling to determine differential gene expression between the permanent mouse articular cartilage and the transient growth plate cartilage, we identified a highly expressed gene, Cilp2, which is expressed differentially by articular chondrocytes. CILP-2 is highly homologous to CILP-1 (cartilage intermediate layer protein 1), which is expressed in the intermediate zone of articular cartilage and has been linked to cartilage degenerative diseases. We demonstrated that Cilp2 has a restricted mRNA distribution at the surface of the mouse articular cartilage during development, becoming localized to the intermediate zone of articular cartilage and meniscal cartilage with maturity. Although the extracellular CILP-2 protein localization is broadly similar to CILP-1, CILP-2 appears to be more localized in the deeper intermediate zone of the articular cartilage extracellular matrix at maturity. CILP-2 was shown to be proteolytically processed, N-glycosylated, and present in human articular cartilage. In surgically induced osteoarthritis in mice, Cilp1 and Cilp2 gene expression was dysregulated. However, whereas Cilp1 expression was increased, Cilp2 gene expression was down-regulated demonstrating a differential response to mechanically induced joint destabilization. CILP-2 protein was reduced in the mouse osteoarthritic cartilage. Ultrastructural analysis also suggested that CILP-2 may be associated with collagen VI microfibrils and thus may mediate interactions between matrix components in the territorial and inter-territorial articular cartilage matrix. mRNA expression analysis indicated that whereas Cilp1 and Cilp2 are expressed most abundantly in cartilaginous tissues, expression can be detected in muscle and heart. During limb development, chondrocytes follow alternative developmental pathways. Chondrocytes that form at the epiphyseal surface of long bones develop into permanent articular chondrocytes and form the smooth articular cartilage necessary for effective weight-bearing and joint movement. The other group of chondrocytes, the transient epiphyseal chondrocytes, are organized into growth plates, and undergo a sequential maturation program from resting cells to proliferative, prehypertrophic, and ultimately hypertrophic end-stage chondrocytes that are replaced with bone during endochondral ossification. Both populations of chondrocytes are critical for the formation of the skeleton and disturbances to normal chondrocyte development and function results in chondrodysplasias (reviewed by Refs. 1-3).One of the important determinants of cartilage function is extracellular matrix (ECM) 3 structure and composition. To identify new ECM determinants of the articular cartilage, we compared the gene expression profile of mouse articular cartilage with growth plate cartilage. These studies revealed that the most highly differentially expressed cDNA on the array was a Riken clone that corresponded to Cilp2 (cartilage intermediatelayer protein, isoform 2), recently reported as a product of cartilage c...

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Section: Discussionmentioning

confidence: 99%

Cartilage Intermediate Layer Protein 2 (CILP-2) Is Expressed in Articular and Meniscal Cartilage and Down-regulated in Experimental Osteoarthritis

Bernardo

Belluoccio

Rowley

et al. 2011

Journal of Biological Chemistry

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“…13 In support of this idea, changes in the distribution, expression, and production of SLRPs in osteoarthritic tissue implicate that SLRP family members may function to maintain normal chondrocyte activity and cartilage tissue integrity. 17,49,50 Specifically, elevated levels of discrete fragmented forms of Bgn, Fmod, and other SLRPs were discovered in patients with degenerating articular cartilage, 50 and generalized proteoglycan loss was apparent in late-stage osteoarthritic cartilage lesions. 49 Simultaneously, as an attempt to repair damaged ECM, chondrocytes increased the production of the SLRPs.…”

Section: Discussionmentioning

confidence: 99%

“…17,49,50 Specifically, elevated levels of discrete fragmented forms of Bgn, Fmod, and other SLRPs were discovered in patients with degenerating articular cartilage, 50 and generalized proteoglycan loss was apparent in late-stage osteoarthritic cartilage lesions. 49 Simultaneously, as an attempt to repair damaged ECM, chondrocytes increased the production of the SLRPs. 14,49,50 These data indicate alterations in the distribution and production of SLRPs could lead to the development of joint degenerative diseases.…”

Section: Discussionmentioning

confidence: 99%

“…49 Simultaneously, as an attempt to repair damaged ECM, chondrocytes increased the production of the SLRPs. 14,49,50 These data indicate alterations in the distribution and production of SLRPs could lead to the development of joint degenerative diseases. Consequently, to study how ECM proteins regulate mandibular condylar cartilage formation and maintenance in the TMJ, we used a mouse model of TMJ OA that is deficient in two SLRPs, Bgn and Fmod.…”

Section: Discussionmentioning

confidence: 99%

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Biglycan and Fibromodulin Have Essential Roles in Regulating Chondrogenesis and Extracellular Matrix Turnover in Temporomandibular Joint Osteoarthritis

Embree

Kilts

Ono

et al. 2010

The American Journal of Pathology

101

110

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The temporomandibular joint is critical for jaw movements and allows for mastication, digestion of food, and speech. Temporomandibular joint osteoarthritis is a degenerative disease that is marked by permanent cartilage destruction and loss of extracellular matrix (ECM). To understand how the ECM regulates mandibular condylar chondrocyte (MCC) differentiation and function, we used a genetic mouse model of temporomandibular joint osteoarthritis that is deficient in two ECM proteins, biglycan and fibromodulin (Bgn Fmod؊/؊ ). Given the unavailability of cell lines, we first isolated primary MCCs and found that they were phenotypically unique from hyaline articular chondrocytes isolated from the knee joint. Using Bgn Fmod؊/؊ MCCs, we discovered the early basis for temporomandibular joint osteoarthritis arises from abnormal and accelerated chondrogenesis. Transforming growth factor (TGF)-␤1 is a growth factor that is critical for chondrogenesis and binds to both biglycan and fibromodulin. Our studies revealed the sequestration of TGF-␤1 was decreased within the ECM of Bgn ؊/0 Fmod ؊/؊ MCCs, leading to overactive TGF-␤1 signal transduction. Using an explant culture system, we found that overactive TGF-␤1 signals induced chondrogenesis and ECM turnover in this model. We demonstrated for the first time a comprehensive study revealing the importance of the ECM in maintaining the mandibular condylar cartilage integrity and identified biglycan and fibromodulin as novel key players in regulating chondrogenesis and ECM turnover during temoporomandibular joint osteoarthritis pathology.

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“…Further, all samples were processed for RNA isolation or placed in fixative within 3 h after isolation from the patient. There are few reported studies which utilize this type of approach in human OA [8,22,50]. Bock et al, reported that the transcription and translation of mRNA for both decorin and biglycan were up-regulated in the maximum loading area of late-stage OA, compared with adjacent areas in order to compensate for the general loss of proteoglycan associated with this stage of the disease [8].…”

Section: Discussionmentioning

confidence: 99%

Intrajoint comparisons of gene expression patterns in human osteoarthritis suggest a change in chondrocyte phenotype

Yagi

McBurney

Laverty

et al. 2005

Journal Orthopaedic Research

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Osteoarthritis (OA) is a degenerative cartilage disease with varying degrees of severity within a given joint. The purpose of this study was to define a sampling procedure for comparing human minimal and advanced OA cartilage in the same patient and to determine basic patterns of gene expression in these regions. A specific hypothesis under study was that the expression level of Bcl-2 would correlate with sox9 and aggrecan mRNA expression in vivo as has been demonstrated in vitro. Femoral condylar advanced OA cartilage was located within 1 cm of overt lesions, and minimal cartilage was taken from areas with no obvious surface defects. Histological sections were scored for disease severity and chondroitin sulfate and hydroxyproline content was determined. The expression level of nine specific genes (aggrecan, collagen type 11, Bcl-2, sox9, Link protein, osteopontin, and MMP-13, -3, and -9) was determined by quantitative real time PCR. The scores for fibrillation, chondrocyte cloning, and proteoglycan depletion were significantly different between advanced and minimal OA cartilage. The advanced OA cartilage had significantly less chondroitin sulfate than the minimal OA cartilage. Osteopontin mRNA expression showed a 3.6-fold increase in advanced compared to minimal OA cartilage. In contrast, the level of mRNA coding for aggrecan, link protein, Bcl-2, sox9 and MMP-3, -9, -13 were all decreased in advanced compared to minimal cartilage in the majority of the patients studied. Collagen type I1 mRNA expression displayed a wide-range of variation. A statistically significant correlation was observed both between Bcl-2 and sox9 mRNA level, and between Bcl-2 and aggrecan mRNA expression. The patient matched comparison of minimal and advanced OA cartilage revealed differences in cellular and tissue characteristics, and changes in gene expression that may be involved in OA progression. In addition, Bcl-2 may also play a role in regulating the expression of aggrecan through sox9 in vivo as well as in vitro.

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The small proteoglycans decorin and biglycan in human articular cartilage of late-stage osteoarthritis

Abstract: The results indicate that at late stages of osteoarthritis the levels of transcription and translation for decorin and biglycan are up-regulated, probably in an effort to compensate for the general proteoglycan loss, characteristic of this disease stage.

Cited by 70 publications

References 30 publications

Cartilage Intermediate Layer Protein 2 (CILP-2) Is Expressed in Articular and Meniscal Cartilage and Down-regulated in Experimental Osteoarthritis

Cartilage Intermediate Layer Protein 2 (CILP-2) Is Expressed in Articular and Meniscal Cartilage and Down-regulated in Experimental Osteoarthritis

Biglycan and Fibromodulin Have Essential Roles in Regulating Chondrogenesis and Extracellular Matrix Turnover in Temporomandibular Joint Osteoarthritis

Intrajoint comparisons of gene expression patterns in human osteoarthritis suggest a change in chondrocyte phenotype

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