Differential Gene Expression in Synovium of Rheumatoid Arthritis and Osteoarthritis

Jüsten, Hans‐Peter; Grünewald, Elisabeth; Totzke, Gudrun; Gouni‐Berthold, Ioanna; Sachinidis, Agapios; Wessinghage, D; Vetter, Hans; Schulze‐Osthoff, Klaus; Ko, Yon

doi:10.1006/mcbr.2000.0211

Cited by 59 publications

(45 citation statements)

References 39 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Interestingly, upregulation of anx2 has been correlated with the joint destruction and pathologic mineralization associated with both rheumatoid and osteoarthritis (Justen et al, 2000;Kirsch et al, 2000). It has been suggested that the progressive breakdown observed in osteoarthritic cartilage may be the result of MV release, enzyme upregulation and abnormal calcification in the joints (Einhorn et al, 1985).…”

Section: Discussionmentioning

confidence: 99%

The role of annexin 2 in osteoblastic mineralization

Gillette

Nielsen-Preiss

2004

Journal of Cell Science

View full text Add to dashboard Cite

While the basic cellular contributions to bone differentiation and mineralization are widely accepted, the regulation of these processes at the intracellular level remains inadequately understood. Our laboratory recently identified annexin 2 as a protein involved in osteoblastic mineralization. Annexin 2 was overexpressed twofold in SaOSLM2 osteoblastic cells as a fusion protein with green fluorescent protein. The overexpression of annexin 2 led to an increase in alkaline phosphatase activity as well as an increase in mineralization. Our data suggest that the increase in alkaline phosphatase activity does not result from increased alkaline phosphatase transcript or protein levels; therefore we evaluated mechanism of action. We determined that both annexin 2 and alkaline phosphatase activity were localized to membrane microdomains called lipid rafts in osteoblastic cells. Annexin 2 overexpression resulted in an increase in alkaline phosphatase activity that was associated with lipid microdomains in a cholesterol-dependent manner. Furthermore, disruption of lipid rafts with a cholesterol sequestering agent or reduction of annexin 2 expression by specific antisense oligonucleotides each resulted in diminished mineralization. Therefore, intact lipid rafts containing annexin 2 appear to be important for alkaline phosphatase activity and may facilitate the osteoblastic mineralization process.

show abstract

Section: Discussionmentioning

confidence: 99%

The role of annexin 2 in osteoblastic mineralization

Gillette

Nielsen-Preiss

2004

Journal of Cell Science

View full text Add to dashboard Cite

show abstract

“…Loss-of-function mutations in the PRG4 gene causes the camptodactyly-arthropathy-coxa vara-pericarditis syndrome in humans, a syndrome of precocious joint failure associated with non-inflammatory synovial hyperplasia and subintimal fibrosis of the joint capsule (3). Lubricin is found heterogeneously expressed in the synovium of rheumatoid arthritis (RA) and osteoarthritis (OA), implying a role in the pathogenesis of these diseases (21,22). RA patients varied with respect to lubricin expression, where the patients with low levels of lubricin had more aggressive joint disease (22).…”

Section: Lubricin (Or Proteoglycan 4 (Prg4)mentioning

confidence: 99%

Human Synovial Lubricin Expresses Sialyl Lewis x Determinant and Has L-selectin Ligand Activity

Jin

Ekwall

Bylund

et al. 2012

Journal of Biological Chemistry

View full text Add to dashboard Cite

Background:Lubricin is an abundant mucin-like glycoprotein in synovial fluid and a major component responsible for joint lubrication. Results: Lewis x and sulfated O-glycans enable lubricin to bind L-selectin. Lubricin binds to polymorphonuclear granulocytes (PMN) in an L-selectin-dependent and -independent manner. Conclusion: PMN isolated from peripheral blood and synovial fluid keep a coat of lubricin. Significance: Lubricin may play a role in PMN-mediated inflammation.

show abstract

“…Increasing evidence has implicated GEP in the regulation of differentiation, development, and pathological processes. It has been isolated as a differentially expressed gene from mesothelial differentiation (85), sexual differentiation of the brain (87), macrophage development (8), and synovium in rheumatoid arthritis and osteoarthritis (55). GEP was also shown to be a crucial mediator of wound response and tissue repair (40,99).…”

mentioning

confidence: 99%

ADAMTS-7, a Direct Target of PTHrP, Adversely Regulates Endochondral Bone Growth by Associating with and Inactivating GEP Growth Factor

Bai

Wang

Kong

et al. 2009

Molecular and Cellular Biology

121

View full text Add to dashboard Cite

ADAMTS-7, a metalloproteinase that belongs to ADAMTS family, is important for the degradation of cartilage extracellular matrix proteins in arthritis. Herein we report that ADAMTS-7 is upregulated during chondrocyte differentiation and demonstrates the temporal and spatial expression pattern during skeletal development. ADAMTS-7 potently inhibits chondrocyte differentiation and endochondral bone formation, and this inhibition depends on its proteolytic activity. The cysteine-rich domain of ADAMTS-7 is required for its interaction with the extracellular matrix, and the C-terminal four-thrombospondin motifs are necessary for its full proteolytic activity and inhibition of chondrocyte differentiation. ADAMTS-7 is an important target of canonical PTHrP signaling, since (i) PTHrP induces ADAMTS-7, (ii) ADAMTS-7 is downregulated in PTHrP null mutant (PTHrP؊/؊) growth plate chondrocytes, and (iii) blockage of ADAMTS-7 almost abolishes PTHrP-mediated inhibition of chondrocyte hypertrophy and endochondral bone growth. ADAMTS-7 associates with granulin-epithelin precursor (GEP), an autocrine growth factor that has been implicated in tissue regeneration, tumorigenesis, and inflammation. In addition, ADAMTS-7 acts as a new GEP convertase and neutralizes GEP-stimulated endochondral bone formation.Collectively, these findings demonstrate that ADAMTS-7, a direct target of PTHrP signaling, negatively regulates endochondral bone formation by associating with and inactivating GEP chondrogenic growth factor.The ADAMTS family consists of secreted zinc metalloproteinases with a precisely ordered modular organization that includes at least one thrombospondin type I repeat (51, 53). Important functions have been established for several members of the ADAMTS family. ADAMTS-1, ADAMTS-4, ADAMTS-5, ADAMTS-8, ADAMTS-9, ADAMTS-16, and ADAMTS-18 degrade the cartilage aggrecan (1,19,36,61,84,88), and ADAMTS-5 plays a primary role in aggrecan loss in arthritis (36, 84). ADAMTS-2, ADAMTS-3, and ADAMTS-14 are procollagen N-propeptidases (18, 30). ADAMTS-2 mutations cause dermatosparaxis, an inherited disorder characterized by severe skin fragility (17). ADAMTS-13 is a von Willebrand factor-cleaving protease, and its mutations lead to heritable life-threatening thrombocytopenic purpura (65). ADAMTS-12 and ADAMTS-7 share the same domain organization and structure and form a subgroup within the ADAMTS family (13, 83). These two enzymes have been found to associate with alpha-2-macroglobulin (13,70,83), and ADAMTS-12 also degrades aggrecan (68). Studies from our group demonstrated that ADAMTS-7 and ADAMTS-12 directly associate with and degrade COMP, a prominent noncollagenous component of cartilage (66,67). COMP is a 524-kDa, pentameric, disulfide-bonded, multidomain glycoprotein composed of approximately equal subunits (ϳ110 kDa each) (43,75). Although the function of COMP is not completely understood, it appears to mediate chondrocyte attachment by an integrin receptor (15,29), and accumulating evidence suggests that COMP may function to stabilize...

show abstract

Differential Gene Expression in Synovium of Rheumatoid Arthritis and Osteoarthritis

Cited by 59 publications

References 39 publications

The role of annexin 2 in osteoblastic mineralization

The role of annexin 2 in osteoblastic mineralization

Human Synovial Lubricin Expresses Sialyl Lewis x Determinant and Has L-selectin Ligand Activity

ADAMTS-7, a Direct Target of PTHrP, Adversely Regulates Endochondral Bone Growth by Associating with and Inactivating GEP Growth Factor

Contact Info

Product

Resources

About