Human articular chondrocytes produce IL-7 and respond to IL-7 with increased production of matrix metalloproteinase-13

Long, David; Blake, S; Song, Xiao Yu; Lark, Michael W.; Loeser, Richard F.

doi:10.1186/ar2376

Cited by 78 publications

(77 citation statements)

References 26 publications

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“…From histological sections, 91%, 77%, and 92%, respectively, of femoral, tibial, and calvarial osteocytes, terminally differentiated cells of the osteogenic lineage (Figures 3D–3F and S3A), and all perilipin-positive bone marrow cells and all adipocytes in white adipose tissue examined were EYFP negative (Figures 3G–3L and S3C). Strong EYFP positivity was confirmed in 11%–60% of articular chondrocytes (Figures 3M–3O and S3A), where IL-7 expression has been previously identified (Long et al., 2008), and in 7%–31% of hypertrophic chondrocytes (Figure S3A). These data demonstrate that a substantial proportion of mesodermal-derived adipose, bone, and cartilage tissues originate from a progenitor cell type that at no point expressed IL-7 and support the existence of poorly/non-differentiating IL-7 hi BMSC subtype in vivo.…”

Section: Resultssupporting

confidence: 72%

Multiparameter Analysis of Human Bone Marrow Stromal Cells Identifies Distinct Immunomodulatory and Differentiation-Competent Subtypes

et al. 2015

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SummaryBone marrow stromal cells (BMSCs, also called bone-marrow-derived mesenchymal stromal cells) provide hematopoietic support and immunoregulation and contain a stem cell fraction capable of skeletogenic differentiation. We used immortalized human BMSC clonal lines for multi-level analysis of functional markers for BMSC subsets. All clones expressed typical BMSC cell-surface antigens; however, clones with trilineage differentiation capacity exhibited enhanced vascular interaction gene sets, whereas non-differentiating clones were uniquely CD317 positive with significantly enriched immunomodulatory transcriptional networks and high IL-7 production. IL-7 lineage tracing and CD317 immunolocalization confirmed the existence of a rare non-differentiating BMSC subtype, distinct from Cxcl12-DsRed+ perivascular stromal cells in vivo. Colony-forming CD317+ IL-7hi cells, identified at ∼1%–3% frequency in heterogeneous human BMSC fractions, were found to have the same biomolecular profile as non-differentiating BMSC clones using Raman spectroscopy. Distinct functional identities can be assigned to BMSC subpopulations, which are likely to have specific roles in immune control, lymphopoiesis, and bone homeostasis.

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Section: Resultssupporting

confidence: 72%

Multiparameter Analysis of Human Bone Marrow Stromal Cells Identifies Distinct Immunomodulatory and Differentiation-Competent Subtypes

et al. 2015

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“…It is produced by OA chondrocytes, and IL-7-stimulated chondrocytes respond with proteoglycan release from cartilage (Long et al 2008). The catabolic properties of IL-7 negatively affect the cartilage in at least 3 ways: inflammation-driven joint destruction, T cell-driven bone loss, and direct, harmful effects on cartilage (van Roon and Lafeber 2008).…”

Section: Discussionmentioning

confidence: 99%

Interleukin-7 levels in synovial fluid increase with age and MMP-1 levels decrease with progression of osteoarthritis

Rübenhagen¹,

Schüttrumpf²,

Stürmer³

et al. 2011

Acta Orthopaedica

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Background and purpose Little is known about biochemical mediators that correlate with the initiation and progression of knee osteoarthritis (OA). We therefore valuated the roles of cytokines and metalloenzymes in knee OA in relation to OA grading, age, and BMI.Patients and methods A multiplex ELISA-based immunoassay (Luminex technology) was used to measure biochemical mediators in the synovial fluid (SF) of 82 patients undergoing knee surgery. All patients were classified according to age, BMI, and OA grade. 24 patients had no signs of OA (knee reconstruction surgeries). The mediators that were tested for included interleukins (IL-1Ra, IL-6, IL-7, and IL-18), chemokines (CCL2 (MCP-1), CCL3 (MIP-1a), and CXCL8 (IL-8)), growth factors (HGF and VEGF), and matrix metalloproteinases (MMP-1, MMP-2, MMP-9, and MMP-13).Results There was a correlation between IL-7 levels in SF and age (p < 0.01). The 11 highest IL-7 levels were seen in patients who were aged between 59 and 72 but had different OA grades. In contrast, all patients who had severe OA in all 3 knee compartments (pan-OA) had only low or medium IL-7 levels. There was a negative correlation between MMP-1 levels in synovial fluid and grade of OA (p < 0.001). Correlation studies between pairs of mediators revealed two groups of mediators that are important in OA progression, dominated by MCP-1 and IL-1Ra.Interpretation IL-7 levels in SF are elevated in elderly people suffering from OA of different grades, but they are depressed in patients with severe 3-compartment OA, possibly due to widely impaired chondrocytes embedded in the affected cartilage tissue. The observed decrease in MMP-1 levels in SF, which is dependent on the severity of OA, may be caused by deterioration of superficial cartilage layers during progression of OA.

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“…The impact of cytokine stimulation on articular cartilage and subsequent extracellular matrix degradation is well documented 7–9 ; however, the role of the meniscus in this process is unclear. The knee joint functions as an organ with a shared environment comprised of cartilage, synovium, ligaments and the meniscus.…”

Section: Introductionmentioning

confidence: 99%

Pro-inflammatory stimulation of meniscus cells increases production of matrix metalloproteinases and additional catabolic factors involved in osteoarthritis pathogenesis

Stone

Loeser

Vanderman

et al. 2014

Osteoarthritis and Cartilage

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Objective Meniscus injury increases the risk of osteoarthritis; however, the biologic mechanism remains unknown. We hypothesized that pro-inflammatory stimulation of meniscus would increase production of matrix-degrading enzymes, cytokines and chemokines which cause joint tissue destruction and could contribute to osteoarthritis development. Design Meniscus and cartilage tissue from healthy tissue donors and total knee arthroplasties was cultured. Primary cell cultures were stimulated with pro-inflammatory factors [IL-1β, IL-6, or fibronectin fragments (FnF)] and cellular responses were analyzed by real-time PCR, protein arrays and immunoblots. To determine if NF-κB was required for MMP production, meniscus cultures were treated with inflammatory factors with and without the NF-κB inhibitor, hypoestoxide. Results Normal and osteoarthritic meniscus cells increased their MMP secretion in response to stimulation, but specific patterns emerged that were unique to each stimulus with the greatest number of MMPs expressed in response to FnF. Meniscus collagen and connective tissue growth factor gene expression was reduced. Expression of cytokines (IL-1α, IL-1β, IL-6), chemokines (IL-8, CXCL1, CXCL2, CSF1) and components of the NF-κB and tumor necrosis factor (TNF) family were significantly increased. Cytokine and chemokine protein production was also increased by stimulation. When primary cell cultures were treated with hypoestoxide in conjunction with pro-inflammatory stimulation, p65 activation was reduced as were MMP-1 and MMP-3 production. Conclusions Pro-inflammatory stimulation of meniscus cells increased matrix metalloproteinase production and catabolic gene expression. The meniscus could have an active biologic role in osteoarthritis development following joint injury through increased production of cytokines, chemokines, and matrix-degrading enzymes.

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Human articular chondrocytes produce IL-7 and respond to IL-7 with increased production of matrix metalloproteinase-13

Cited by 78 publications

References 26 publications

Multiparameter Analysis of Human Bone Marrow Stromal Cells Identifies Distinct Immunomodulatory and Differentiation-Competent Subtypes

Multiparameter Analysis of Human Bone Marrow Stromal Cells Identifies Distinct Immunomodulatory and Differentiation-Competent Subtypes

Interleukin-7 levels in synovial fluid increase with age and MMP-1 levels decrease with progression of osteoarthritis

Pro-inflammatory stimulation of meniscus cells increases production of matrix metalloproteinases and additional catabolic factors involved in osteoarthritis pathogenesis

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