Expression of alpha  and beta  subunits of the integrin superfamily in articular cartilage from macroscopically normal and osteoarthritic human femoral heads

Østergaard, Keld; Salter, Donald; Petersen, Jørgen Holm; Bendtzen, Klaus; Hvolris, Jesper; Andersen, Claus B

doi:10.1136/ard.57.5.303

Cited by 78 publications

(74 citation statements)

References 40 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Nonetheless, ␣v␤5 integrin could be another important integrin in chondrocytes. The results of previous studies, along with the findings of the present study, consistently indicate that ␣v␤5 integrin is abundantly expressed on articular chondrocytes (19,20) and that ␣v␤5 integrin mediates chondrocyte attachment to various matrices (45,46). Therefore, it would not be surprising to find that ␣v␤5 integrin is involved in the metabolic and morphologic changes that occur in monolayer-cultured chondrocytes after plating.…”

Section: Discussionsupporting

confidence: 88%

“…(Data are available online at http://www.hosp.go.jp/ϳsagami/rinken/crc/index.html.) Although the microarray used for the analysis did not contain the probe for ␣1 integrin, previous studies have shown that it is a dominant integrin in human articular chondrocytes (19,20,28). Thus, we focused our investigation on the significance of these 11 integrins in the dedifferentiation of monolayer-cultured articular chondrocytes.…”

Section: Determination Of Dominant Integrins In Human Articular Chondmentioning

confidence: 99%

“…Integrins are present on the cell surface in heterodimers of specific combinations of ␣ and ␤ integrin molecules and mediate dynamic interactions between the cell and the immediately surrounding environment (16). Chondrocytes express several types of integrins (17)(18)(19)(20), which are known to regulate various aspects of cell behavior. In addition to cell attachment, integrins on the chondrocytes are involved in proliferation, survival, differentiation, matrix remodeling, and response to mechanical stimuli (21)(22)(23)(24)(25).…”

mentioning

confidence: 99%

See 2 more Smart Citations

αvβ5 Integrin promotes dedifferentiation of monolayer-cultured articular chondrocytes

Fukui¹,

Ikeda²,

Tanaka³

et al. 2011

Arthritis & Rheumatism

View full text Add to dashboard Cite

Objective. When cultured in monolayers, articular chondrocytes undergo an obvious phenotypic change. Although the involvement of integrins has been suggested, the exact mechanisms of the change have not been determined. This study was undertaken to clarify the mechanisms underlying the loss of chondrocyte phenotype early after plating.Methods. Primary cultured human articular chondrocytes were used for the experiments. Involvement of respective integrins in the phenotypic change was investigated in RNA interference (RNAi) experiments. A signaling pathway involved in the change was identified in experiments using specific inhibitors and adenoviruses encoding mutated genes involved in the pathway. Adenoviruses carrying mutated GTPases were used to determine the involvement of small GTPases in the process.Results. In monolayer-cultured chondrocytes, suppression of ␣v or ␤5 integrin expression by RNAi inhibited morphologic changes in the cells and increased (or prevented a reduction in) the expression of various cartilage matrix genes. Consistent results were obtained in experiments using a blocking antibody and a synthetic inhibitor of ␣v␤5 integrin. The decrease in cartilage matrix gene expression in chondrocytes after plating was mediated by ERK signaling, which was promoted primarily by ␣v␤5 integrin. In articular chondrocytes, the affinity of ␣v␤5 integrin for ligands was regulated by the small GTPase R-Ras. R-Ras was gradually activated in monolayer-cultured chondrocytes after plating, which caused a gradual decline in cartilage matrix gene expression through enhanced ␣v␤5 integrin activation and the subsequent increase in ERK signaling.Conclusion. Our findings indicate that ␣v␤5 integrin may be involved in the change that occurs in monolayer-cultured chondrocytes after plating.

show abstract

Section: Discussionsupporting

confidence: 88%

Section: Determination Of Dominant Integrins In Human Articular Chondmentioning

confidence: 99%

mentioning

confidence: 99%

See 1 more Smart Citation

αvβ5 Integrin promotes dedifferentiation of monolayer-cultured articular chondrocytes

Fukui¹,

Ikeda²,

Tanaka³

et al. 2011

Arthritis & Rheumatism

View full text Add to dashboard Cite

show abstract

“…The present study cannot exclude the possibility that HA-CD44 interaction could inhibit the action of HBFN-f through binding to other receptor(s) on chondrocytes. Integrin α4β1 is expressed on chondrocytes in OA cartilage (17,27) but not normal (27). As shown in our previous studies in RA synovial fibroblasts (42), HBFN-f may act through this integrin in OA and RA chondrocytes.…”

Section: Correlation Of Cd44 Levels With Hbfn-f-stimulated No Productmentioning

confidence: 78%

Comparison of hyaluronan effects among normal, osteoarthritis, and rheumatoid arthritis cartilages stimulated with fibronectin fragment

Yasuda

2010

Biomed. Res.

View full text Add to dashboard Cite

High molecular weight hyaluronan (HA) is widely used in the treatment of osteoarthritis (OA) and rheumatoid arthritis (RA) by intra-articular injection. However, comparative studies of HA actions on catalytically activated cartilages in different pathologic conditions have rarely been investigated. This study was aimed to compare the inhibitory effects of HA on nitric oxide (NO) production by COOH-terminal heparin-binding fibronectin fragment (HBFN-f) between normal and diseased cartilages. When articular cartilage explants from normal, OA, or RA joints were incubated with HBFN-f, the RA and OA cartilages produced higher levels of NO compared with normal cartilage. Pretreatment with 2700 kDa HA resulted in significant suppression of HBFN-f-stimulated NO production in OA and RA cartilages. While CD44 was up-regulated in OA and RA cartilages, anti-CD44 antibody reversed HA inhibition of HBFN-f action in those cartilages. The present results clearly demonstrated that HA blocked HBFN-f actions in OA and RA cartilages through interaction with CD44. HA, which targets CD44 highly expressed on OA and RA chondrocytes, could suppress catabolic actions by fibronectin fragments like HBFN-f in diseased cartilage.Fibronectin (FN) is a component of normal cartilage matrix. FN consists predominantly of three types of homologous repeating segments (designated I, II, and III). While FN is encoded by a single gene, significant protein heterogeneity results from alternative RNA splicing at three sites, termed Extra type III Domain A (ED-A), Extra type III Domain B (ED-B), and the variable (V) region. The V region is also referred to as the connecting segment between III14-15 (IIICS). There are 10 principal isoforms predicted by RNA splicing patterns, each of which contains amino (NH 2 )-terminal heparin-, gelatin-, cell-and carboxyl (COOH)-terminal heparinbinding domains. Elevated levels of FN are found in osteoarthritic cartilage (12, 21) and in both synovial fluid and plasma of osteoarthritis (OA) and rheumatoid arthritis (RA) (29,34). FN is readily degraded into fragments by proteinases. In OA and RA, activation of extracellular proteolysis may lead to the fragmentation of FN. Indeed, increased levels of 30-200 kDa fibronectin fragments (FN-fs) are found in cartilage and synovial fluid from patients with OA and RA (9, 34). Native FN has no catabolic effect on cartilage. Once FN is fragmented, those proteolytic fragments acquire catalytic activities whereby increased FN-fs are thought to cause cartilage destruction in OA and RA (35). Of FN-fs, the fragments with the central cell-, NH 2 -terminal heparin-and NH 2 -terminal gelatin-binding domains have been extensively investigated. Those FN-fs can stimulate proteoglycan breakdown in cultured articular cartilage explants (8). We have recently found that another FN-f, 40 kDa COOH-terminal heparin-binding fragment containing both the III12-14 and IIICS domains (HBFN-f), enhances type II collagen cleavage by collagenase in association with enhanced production

show abstract

“…In adult joints, increased immunostaining of ␤1 integrin was reported in osteoarthritic monkey cartilage compared with normal cartilage (14) and in human OA samples at minimally damaged locations compared with areas with more severe lesions (15). In another study, the neoexpression of ␣2, ␣4, and ␤2 integrins was observed in osteoarthritic human femoral head cartilage (16). In vitro experiments have suggested that signaling through the fibronectin (FN) receptor ␣5␤1 integrin is pivotal to prevent cell death of normal and osteoarthritic human articular chondrocytes (17).…”

Section: -Col2a1crementioning

confidence: 82%

β1 Integrin Deficiency Results in Multiple Abnormalities of the Knee Joint

Raducanu

Hunziker

Drosse³

et al. 2009

Journal of Biological Chemistry

View full text Add to dashboard Cite

The lack of ␤1 integrins on chondrocytes leads to severe chondrodysplasia associated with high mortality rate around birth. To assess the impact of ␤1 integrin-mediated cell-matrix interactions on the function of adult knee joints, we conditionally deleted the ␤1 integrin gene in early limb mesenchyme using the Prx1-cre transgene. Mutant mice developed short limbed dwarfism and had joint defects due to ␤1 integrin deficiency in articular regions. The articular cartilage (AC) was structurally disorganized, accompanied by accelerated terminal differentiation, altered shape, and disrupted actin cytoskeleton of the chondrocytes. Defects in chondrocyte proliferation, cytokinesis, and survival resulted in hypocellularity. However, no significant differences in cartilage erosion, in the expression of matrix-degrading proteases, or in the exposure of aggrecan and collagen II cleavage neoepitopes were observed between control and mutant AC. We found no evidence for disturbed activation of MAPKs (ERK1/2, p38, and JNK) in vivo. Furthermore, fibronectin fragment-stimulated ERK activation and MMP-13 expression were indistinguishable in control and mutant femoral head explants. The mutant synovium was hyperplastic and frequently underwent chondrogenic differentiation. ␤1-null synoviocytes showed increased proliferation and phospho-focal adhesion kinase expression. Taken together, deletion of ␤1 integrins in the limb bud results in multiple abnormalities of the knee joints; however, it does not accelerate AC destruction, perturb cartilage metabolism, or influence intracellular MAPK signaling pathways. Chondrocytes of the articular cartilage (AC)2 secrete a unique set of extracellular matrix (ECM) molecules that assemble into interactive associates composed of collagens, proteoglycans (PGs), and non-collagenous glycoproteins (1). The fibrillar collagen meshwork supplies cartilage with its tensile strength, whereas the hydrated glycosaminoglycan (GAG) chains of PGs (mainly aggrecan) generate an osmotic swelling pressure that resists compressive forces. In diarthrodial joints, the molecular composition and the physical properties of the cartilage are principal determinants for the shock-absorbing function of articular surfaces upon mechanical loading. During the development of osteoarthritis (OA), an imbalance between anabolic and catabolic processes increases the proteolysis of PGs and collagens (2, 3), which eventually leads to the mechanical weakening of the AC and culminates in its progressive destruction. Physiological and pathological remodeling of the AC ECM is primarily attributed to the activities of matrix metalloproteinases (MMPs) and a disintegrin and metalloproteinase with thrombospondin-like repeat (ADAMTS) proteases (4, 5) and is controlled by the communication between the cells and their environment.An increasing amount of evidence suggests that interactions between chondrocytes and the ECM through the integrin family of heterodimeric (␣␤) transmembrane receptors play a central role in cartilage function (6). Int...

show abstract

Expression of alpha and beta subunits of the integrin superfamily in articular cartilage from macroscopically normal and osteoarthritic human femoral heads

Cited by 78 publications

References 40 publications

αvβ5 Integrin promotes dedifferentiation of monolayer-cultured articular chondrocytes

αvβ5 Integrin promotes dedifferentiation of monolayer-cultured articular chondrocytes

Comparison of hyaluronan effects among normal, osteoarthritis, and rheumatoid arthritis cartilages stimulated with fibronectin fragment

β1 Integrin Deficiency Results in Multiple Abnormalities of the Knee Joint

Contact Info

Product

Resources

About