Stimulation of matrix metalloprotease 3 release from human chondrocytes by the interaction of stromal cell-derived factor 1 and CXC chemokine receptor 4

Kanbe, Katsuaki; Takagishi, Kenji; Chen, Qian

doi:10.1002/1529-0131(200201)46:1<130::aid-art10020>3.0.co;2-d

Cited by 187 publications

(230 citation statements)

References 16 publications

Supporting

Mentioning

212

Contrasting

Unclassified

Order By: Relevance

“…BML MSCs may indeed be recruited to more damaged areas of cartilage and superficial subchondral bone due to higher concentrations of SDF‐1 in these regions, which is the result of diffusion to subchondral bone from OA synovial fluid via thinned, damaged cartilage 38, 39. Our data suggest that once at the site of damage, MSC CXCR4 expression may be down‐regulated to prevent further migration.…”

Section: Discussionmentioning

confidence: 80%

Mesenchymal Stem Cell Alterations in Bone Marrow Lesions in Patients With Hip Osteoarthritis

Campbell

Churchman

Gómez

et al. 2016

Arthritis & Rheumatology

100

106

View full text Add to dashboard Cite

ObjectiveIn patients with osteoarthritis (OA), bone marrow lesions (BMLs) are intimately linked to disease progression. We hypothesized that aberrant multipotential stromal cell (also known as mesenchymal stem cell [MSC]) responses within bone tissue contributes to BML pathophysiology. The aim of this study was to investigate BML and non‐BML native subchondral bone MSCs for numeric, topographic, in vitro functional, and gene expression differences.MethodsEx vivo 3T magnetic resonance imaging (MRI) of the femoral heads of 20 patients with hip OA was performed. MRI‐determined BML and non‐BML regions were excised and enzymatically treated to extract cells and quantify MSCs using flow cytometry and colony‐forming unit–fibroblast (CFU‐F) assay. Immunohistochemical analysis was performed to determine in vivo CD271+ MSC distribution. Culture‐expanded CD271+ cells were analyzed for tripotentiality and gene expression.ResultsBML regions were associated with greater trabecular bone area and cartilage damage compared with non‐BML regions. The proportion of CD45−CD271+ MSCs was higher in BML regions compared with non‐BML regions (median difference 5.6‐fold; P < 0.001); the CFU‐F assay showed a similar trend (median difference 4.3‐fold; P = 0.013). Immunohistochemistry revealed CD271+ cell accumulation in bone adjacent to cartilage defects and areas of osteochondral angiogenesis. BML MSCs had lower proliferation and mineralization capacities in vitro and altered expression of TNFSF11/RANKL and CXCR4/stromal cell–derived factor 1 receptor. OA MSCs showed up‐regulated transcripts for CXCR1 and CCR6 compared with MSCs derived from healthy or osteoporotic bone.ConclusionThis study is the first to show numeric and topographic alterations in native MSCs in the diseased bone of patients with hip OA. Given the associated functional perturbation of MSCs, these data suggest that subchondral bone MSC manipulation may be an OA treatment target.

show abstract

Section: Discussionmentioning

confidence: 80%

Mesenchymal Stem Cell Alterations in Bone Marrow Lesions in Patients With Hip Osteoarthritis

Campbell

Churchman

Gómez

et al. 2016

Arthritis & Rheumatology

100

106

View full text Add to dashboard Cite

show abstract

“…A potentially important role is its ability to modulate the bioactivity of chemokines such as stromal cell-derived factor 1 (SDF-1 or CXCL12) and RANTES. SDF-1 interacts with its unique receptor, CXCR4, and stimulates angiogenesis and mononuclear cell trafficking into the joint as well as MMP-3, MMP-9, and MMP-13 release from chondrocytes (123)(124)(125). DPP-4-mediated removal of the N-terminal dipeptide of SDF-1 reduces leukocyte chemotaxis (122), and this cleavage significantly alters the functionality of the SDF-1:CXCR4 axis (126).…”

Section: Dppsmentioning

confidence: 99%

Emerging roles of serine proteinases in tissue turnover in arthritis

Milner

Patel

Rowan

2008

Arthritis & Rheumatism

View full text Add to dashboard Cite

“…[9][10][11] Elevated levels of CXCL12 were found in patients with multiple sclerosis, inflammatory myopathies, spondyloarthropathies and RA. [12][13][14][15][16][17] Levels of CXCL12 in the synovial fluid of RA patients are around 10 times higher than in healthy joints and reach a mean of 750 ng ml À1 . 16 It is understood that CXCL12 drives chronic inflammation by attraction of monocytes and lymphocytes into the joint and by stimulation of SFs to produce pro-inflammatory cytokines.…”

Section: Introductionmentioning

confidence: 99%

“…[12][13][14][15][16][17] Levels of CXCL12 in the synovial fluid of RA patients are around 10 times higher than in healthy joints and reach a mean of 750 ng ml À1 . 16 It is understood that CXCL12 drives chronic inflammation by attraction of monocytes and lymphocytes into the joint and by stimulation of SFs to produce pro-inflammatory cytokines. [17][18][19][20] Previous studies also showed that cultured RASFs produce more CXCL12 than NSFs or OASFs.…”

Section: Introductionmentioning

confidence: 99%

DNA methylation regulates the expression of CXCL12 in rheumatoid arthritis synovial fibroblasts

et al. 2011

View full text Add to dashboard Cite

In the search for specific genes regulated by DNA methylation in rheumatoid arthritis (RA), we investigated the expression of CXCL12 in synovial fibroblasts (SFs) and the methylation status of its promoter and determined its contribution to the expression of matrix metalloproteinases (MMPs). DNA was isolated from SFs and methylation was analyzed by bisulfite sequencing and McrBC assay. CXCL12 protein was quantified by enzyme-linked immunosorbent assay before and after treatment with 5-azacytidine. RASFs were transfected with CXCR7-siRNA and stimulated with CXCL12. Expression of MMPs was analyzed by real-time PCR. Basal expression of CXCL12 was higher in RASFs than osteoarthritis (OA) SFs. 5-azacytidine demethylation increased the expression of CXCL12 and reduced the methylation of CpG nucleotides. A lower percentage of CpG methylation was found in the CXCL12 promoter of RASFs compared with OASFs. Overall, we observed a significant correlation in the mRNA expression and the CXCL12 promoter DNA methylation. Stimulation of RASFs with CXCL12 increased the expression of MMPs. CXCR7 but not CXCR4 was expressed and functional in SFs. We show here that RASFs produce more CXCL12 than OASFs due to promoter methylation changes and that stimulation with CXCL12 activates MMPs via CXCR7 in SFs. Thereby we describe an endogenously activated pathway in RASFs, which promotes joint destruction.

show abstract

Stimulation of matrix metalloprotease 3 release from human chondrocytes by the interaction of stromal cell-derived factor 1 and CXC chemokine receptor 4

Cited by 187 publications

References 16 publications

Mesenchymal Stem Cell Alterations in Bone Marrow Lesions in Patients With Hip Osteoarthritis

Mesenchymal Stem Cell Alterations in Bone Marrow Lesions in Patients With Hip Osteoarthritis

Emerging roles of serine proteinases in tissue turnover in arthritis

DNA methylation regulates the expression of CXCL12 in rheumatoid arthritis synovial fibroblasts

Contact Info

Product

Resources

About