Haem oxygenase-1 down-regulates high mobility group box 1 and matrix metalloproteinases in osteoarthritic synoviocytes

García-Arnandis, Isabel; Guillén, Marı́a Isabel; Castejón, Miguel Angel; Gomar, F.; Alcaraz, Marı́a José

doi:10.1093/rheumatology/kep463

Cited by 27 publications

(23 citation statements)

References 34 publications

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“…CSPCs have been observed in human, equine 54 and bovine 11 articular cartilage. Identification, isolation and characterization of CSPCs have been based on a | expression of stem-cell-related surface markers (individually and in combination, under various conditions) and b | properties such as clonogenicity and multipotency.…”

Section: Figurementioning

confidence: 99%

“…31 For example, high mobility group protein B1 (HMGB1) released by OA synoviocytes has been implicated as a biochemical mediator of inflammation, acting in cooperation with IL-1β. 31,54 Other soluble factors could also enhance the chemotactic activity of chondrocytes, such as insulin-like growth factor 1 (IGF-1) in serum 55 and platelet-derived growth factor (PDGF) 55,56 in synovial fluid 57 or post-traumatic bleeding. 58,59 Thus, migration of CPCs is likely to be regulated by multiple tissue-injury-related signals.…”

Section: Function Of Cspcs In Cartilage Repairmentioning

confidence: 99%

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Origin and function of cartilage stem/progenitor cells in osteoarthritis

2014

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Articular cartilage is a physiologically non-self-renewing avascular tissue with a singular cell type, the chondrocyte, which functions as the load-bearing surface of the arthrodial joint. Injury to cartilage often progresses spatiotemporally from the articular surface to the subchondral bone, leading to development of degenerative joint diseases such as osteoarthritis (OA). Although lacking intrinsic reparative ability, articular cartilage has been shown to contain a population of stem cells or progenitor cells, similar to those found in many other adult tissues, that are thought to be involved in the maintenance of tissue homeostasis. These so-called cartilage-derived stem/progenitor cells (CSPCs) have been observed in human, equine and bovine articular cartilage, and have been identified, isolated and characterized on the basis of expression of stem-cell-related surface markers, clonogenicity and multilineage differentiation ability. However, the origin and functions of CSPCs are incompletely understood. We review here the current status of CSPC research and discuss the possible origin of these cells, what role they might have in cartilage repair, and their therapeutic potential in OA.

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Section: Figurementioning

confidence: 99%

Section: Function Of Cspcs In Cartilage Repairmentioning

confidence: 99%

Origin and function of cartilage stem/progenitor cells in osteoarthritis

2014

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“…Biliverdin and CO have anti-inflammatory properties. Increasing evidence suggests that loss of HO-1 increases HMGB1 release, whereas upregulation of HO-1 inhibits HMGB1 release in response to inflammatory stimulus (Chen et al, 2013b; Clerigues et al, 2012; Garcia-Arnandis et al, 2010a; Gong et al, 2008; Jang et al, 2012; Park et al, 2013; Sakai et al, 2012; Tsoyi et al, 2009; Wang et al, 2013g; Yun et al, 2010). …”

Section: Hmgb1 Releasementioning

confidence: 99%

“…CXCR3 −/− , but not CCR1 −/− , CCR5 −/− mice and NK cell-depleted mice display severe liver damage after CCl4 injection partly through increased HMGB1 expression in the liver (Zaldivar et al, 2012); HO1 −/− mice show increased mortality in sepsis partly through increased HMGB1 expression in response to LPS or IL-1β (Garcia-Arnandis et al, 2010a; Takamiya et al, 2009); PI3Kγ −/− mice ameliorated the LPS-induced decrease in myocardial contractility and HMGB1 mycocardial expression (Xu et al, 2010); Single-Ig-interleukin-1 related receptor (SIGIRR) −/− mice show cognitive deficiencies and hippocampal dysfunction with enhanced expression of HMGB1 (Costello et al, 2011); Metalloproteinase Zmpste24 −/− mice exhibit lipodystrophy with upregulated HMGB1 expression (Peinado et al, 2011). …”

Section: Hmgb1 Transcriptional Regulation (Figure 8)mentioning

confidence: 99%

HMGB1 in health and disease

Kang

Chen

Zhang

et al. 2014

Molecular Aspects of Medicine

801

828

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Complex genetic and physiological variations as well as environmental factors that drive emergence of chromosomal instability, development of unscheduled cell death, skewed differentiation, and altered metabolism are central to the pathogenesis of human diseases and disorders. Understanding the molecular bases for these processes is important for the development of new diagnostic biomarkers, and for identifying new therapeutic targets. In 1973, a group of non-histone nuclear proteins with high electrophoretic mobility was discovered and termed High-Mobility Group (HMG) proteins. The HMG proteins include three superfamilies termed HMGB, HMGN, and HMGA. High-mobility group box 1 (HMGB1), the most abundant and well-studied HMG protein, senses and coordinates the cellular stress response and plays a critical role not only inside of the cell as a DNA chaperone, chromosome guardian, autophagy sustainer, and protector from apoptotic cell death, but also outside the cell as the prototypic damage associated molecular pattern molecule (DAMP). This DAMP, in conjunction with other factors, thus has cytokine, chemokine, and growth factor activity, orchestrating the inflammatory and immune response. All of these characteristics make HMGB1 a critical molecular target in multiple human diseases including infectious diseases, ischemia, immune disorders, neurodegenerative diseases, metabolic disorders, and cancer. Indeed, a number of emergent strategies have been used to inhibit HMGB1 expression, release, and activity in vitro and in vivo. These include antibodies, peptide inhbitiors, RNAi, anti-coagulants, endogenous hormones, various chemical compounds, HMGB1-receptor and signaling pathway inhibition, artificial DNAs, physical strategies including vagus nerve stimulation and other surgical approaches. Future work further investigating the details of HMGB1 localizationtion, structure, post-translational modification, and identifccation of additional partners will undoubtedly uncover additional secrets regarding HMGB1’s multiple functions.

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“…Nevertheless, the pro-inflammatory activity of HMGB1 in synoviocytes and its participation in synovitis during OA remain to be determined. We have recently reported that HMGB1 is released by OA synoviocytes after activation with IL-1β [16], suggesting the participation of HMGB1 in the inflammatory response induced by this cytokine. In the present study, we further investigated the role of HMGB1 in OA synovial inflammation.…”

Section: Introductionmentioning

confidence: 99%

High mobility group box 1 potentiates the pro-inflammatory effects of interleukin-1β in osteoarthritic synoviocytes

et al. 2010

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IntroductionHigh mobility group box 1 (HMGB1) is released by necrotic cells or secreted in response to inflammatory stimuli. Extracellular HMGB1 may act as a pro-inflammatory cytokine in rheumatoid arthritis. We have recently reported that HMGB1 is released by osteoarthritic synoviocytes after activation with interleukin-1beta (IL-1β) The present study investigated the role of HMGB1 in synovial inflammation in osteoarthritis (OA).MethodsHMGB1 was determined in human synovium using immunohistochemistry, comparing normal to OA. OA synoviocytes were incubated with HMGB1 at 15 or 25 ng/ml in the absence or presence of IL-1β (10 ng/ml). Gene expression was analyzed by quantitative PCR and protein expression by Western Blot and ELISA. Matrix metalloproteinase (MMP) activity was studied by fluorometric procedures and nuclear factor (NF)-κB activation by transient transfection with a NF-κB-luciferase plasmid.ResultsIn the normal synovium, HMGB1 was found in the synovial lining cells, sublining cells, and in the vascular wall cells. The distribution of HMGB1 in OA synovium was similar but the number of HMGB1 positive cells was higher and HMGB1 was also present in infiltrated cells. In normal synovial membrane cells, HMGB1 was found mostly in the nuclei, whereas in OA, HMGB1 was generally found mostly in the cytoplasm. In OA synoviocytes, HMGB1 alone at concentrations of 15 or 25 ng/ml did not affect the production of IL-6, IL-8, CCL2, CCL20, MMP-1 or MMP-3, but in the presence of IL-1β, a significant potentiation of protein and mRNA expression, as well as MMP activity was observed. HMGB1 also enhanced the phosphorylated ERK1/2 and p38 levels, with a lower effect on phosphorylated Akt. In contrast, JNK1/2 phosphorylation was not affected. In addition, HMGB1 at 25 ng/ml significantly potentiated NF-κB activation in the presence of IL-1β.ConclusionsOur results indicate that HMGB1 is overexpressed in OA synovium and mostly present in extracellular form. In OA synoviocytes, HMGB1 cooperates with IL-1β to amplify the inflammatory response leading to the production of a number of cytokines, chemokines and MMPs. Our data support a pro-inflammatory role for this protein contributing to synovitis and articular destruction in OA.

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Haem oxygenase-1 down-regulates high mobility group box 1 and matrix metalloproteinases in osteoarthritic synoviocytes

Abstract: We have provided direct evidence that HO-1 down-regulates MMP-1, -3 and HMGB1 in osteoarthritic synoviocytes. HO-1 may be a potential strategy to control inflammatory and degradative processes in the progression of OA.

Cited by 27 publications

References 34 publications

Origin and function of cartilage stem/progenitor cells in osteoarthritis

Origin and function of cartilage stem/progenitor cells in osteoarthritis

HMGB1 in health and disease

High mobility group box 1 potentiates the pro-inflammatory effects of interleukin-1β in osteoarthritic synoviocytes

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