RAGE and its ligands in bone metabolism

Zhou, Zheng; Xiong, Wen-Cheng

doi:10.2741/s185

Cited by 29 publications

(25 citation statements)

References 69 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It has been suggested that S100A6 could be involved in cell survival by interaction with advanced glycation end products (RAGE), consequent formation of reactive oxygen species (ROS), activation of ERK pathway and changes in NF-κB transcriptional activity, as well as promoting catabolic process in the cartilage 30, 31 . S100A6 was also described to enhance osteoblast proliferation and bone remodelling, however the underlying mechanisms are still unclear 32 . Therefore, our results suggest a potential value of this protein for diagnosis of OA, and underline the need of further functional studies to elucidate the specific role of S100A6 in OA.…”

Section: Discussionmentioning

confidence: 99%

Discovery of circulating proteins associated to knee radiographic osteoarthritis

Lourido

Ayoglu

Fernández‐Tajes

et al. 2017

Sci Rep

View full text Add to dashboard Cite

Currently there are no sufficiently sensitive biomarkers able to reflect changes in joint remodelling during osteoarthritis (OA). In this work, we took an affinity proteomic approach to profile serum samples for proteins that could serve as indicators for the diagnosis of radiographic knee OA. Antibody suspension bead arrays were applied to analyze serum samples from patients with OA (n = 273), control subjects (n = 76) and patients with rheumatoid arthritis (RA, n = 244). For verification, a focused bead array was built and applied to an independent set of serum samples from patients with OA (n = 188), control individuals (n = 83) and RA (n = 168) patients. A linear regression analysis adjusting for sex, age and body mass index (BMI) revealed that three proteins were significantly elevated (P < 0.05) in serum from OA patients compared to controls: C3, ITIH1 and S100A6. A panel consisting of these three proteins had an area under the curve of 0.82 for the classification of OA and control samples. Moreover, C3 and ITIH1 levels were also found to be significantly elevated (P < 0.05) in OA patients compared to RA patients. Upon validation in additional study sets, the alterations of these three candidate serum biomarker proteins could support the diagnosis of radiographic knee OA.

show abstract

Section: Discussionmentioning

confidence: 99%

Discovery of circulating proteins associated to knee radiographic osteoarthritis

Lourido

Ayoglu

Fernández‐Tajes

et al. 2017

Sci Rep

View full text Add to dashboard Cite

show abstract

“…HMGB1, a nuclear protein released from stressed cells, has been indicated as a bone-active cytokine [ 17 ] and involved in ossification, arthritis and ectopic mineralization pathogenesis [ 18 , 31 ]. However, its role in promoting MVs secretion and the mechanism involved remain unknown.…”

Section: Discussionmentioning

confidence: 99%

HMGB1 Induces Secretion of Matrix Vesicles by Macrophages to Enhance Ectopic Mineralization

et al. 2016

View full text Add to dashboard Cite

Numerous clinical conditions have been linked to ectopic mineralization (EM). This process of pathological biomineralization is complex and not fully elucidated, but thought to be started within matrix vesicles (MVs). We hypothesized that high mobility group box 1 (HMGB1), a cytokine associated with biomineralizing process under physiological and pathological conditions, induces EM via promoting MVs secretion from macrophages. In this study, we found that HMGB1 significantly promoted secretion of MVs from macrophages and subsequently led to mineral deposition in elevated Ca/Pi medium in vitro. Transmission electron microscopy of calcifying MVs showed formation of hydroxyapatite crystals in the vesicle interior. Subcutaneous injection into mice with MVs derived from HMGB1-treated cells showed a greater potential to initiate regional mineralization. Mechanistic experiments revealed that HMGB1 activated neutral sphingomyelinase2 (nSMase2) that involved the receptor for advanced glycation end products (RAGE) and p38 MAPK (upstream of nSMase2). Inhibition of nSMase2 with GW4869 or p38 MAPK with SB-239063 prevented MVs secretion and mineral deposition. Collectively, HMGB1 induces MVs secretion from macrophages at least in part, via the RAGE/p38 MAPK/nSMase2 signaling pathway. Our findings thus reveal a novel mechanism by which HMGB1 induces ectopic mineralization.

show abstract

“…We suggest, therefore, that RAGE and HMGB1 regulate bone remodeling in chronic inflammation via up-regulation of the IL-8 production, a mediator of bone destruction, in tissue samples of cholesteatoma. The role of RAGE/HMGB1 interactions in bone remodeling has been reviewed [ 30 ], and a higher expression of RAGE within cholesteatoma perimatrix, which is adjacent to ossicle surface or to other parts of the temporal bone, might be interpreted as indicative of the RAGE/HMGB1 involvement in this process.…”

Section: Discussionmentioning

confidence: 99%

Molecular signaling of the HMGB1/RAGE axis contributes to cholesteatoma pathogenesis

et al. 2014

View full text Add to dashboard Cite

Cholesteatoma represents progressive expansion of the keratinizing squamous epithelium in the middle ear with subsequent chronic inflammation in subepithelial connective tissues. The hypothesis was tested that receptor for advanced glycation endproduct (RAGE) and its ligand, high-mobility box 1 (HMGB1), are overexpressed in cholesteatoma, and the RAGE/HMGB1 axis might contribute to its pathogenesis. Cholesteatoma samples (n = 36) and 27 normal skin specimens were studied by immunohistochemistry (IHC) for HMGB1 and RAGE expression. Effects of HMGB1 signaling on proliferation, migration, cytokine production, and apoptosis of human immortalized keratinocytes (HaCaTs) and normal keratinocytes were studied by quantitative reverse transcription (qRT)-PCR, IHC, Western blots, and flow cytometry after cell co-incubation with HMGB1. While all studied tissues expressed HMGB1, its expression was higher in cholesteatoma than in normal skin (p < 0.0001). All cases of cholesteatoma also showed elevated RAGE expression levels, and only 7/27 (26 %) of normal skin specimens were weakly positive for RAGE. Proliferation and migration of HaCaT cells incubated with HMGB1 were up-regulated (p < 0.05). HMGB1 also prevented HaCaT cell apoptosis and induced activation of several molecular signaling pathways in keratinocytes. The data suggest that in cholesteatoma, HMGB1 released from stressed or necrotic epithelial cells and binding to RAGE overexpressed in keratinocytes initiates molecular signaling that culminates in pro-inflammatory cytokine release and chronic inflammation.Key messageHMGB1 signaling engages multiple activation pathways in RAGE-positive keratinocytes.HMGB1 protects RAGE-positive keratinocytes from drug-induced apoptosis.Keratinocyte proliferation is controlled via RAGE and HMGB1 molecular signaling.Molecular signaling of the HMGB1/RAGE axis contributes to cholesteatoma pathogenesis.Electronic supplementary materialThe online version of this article (doi:10.1007/s00109-014-1217-3) contains supplementary material, which is available to authorized users.

show abstract

RAGE and its ligands in bone metabolism

Cited by 29 publications

References 69 publications

Discovery of circulating proteins associated to knee radiographic osteoarthritis

Discovery of circulating proteins associated to knee radiographic osteoarthritis

HMGB1 Induces Secretion of Matrix Vesicles by Macrophages to Enhance Ectopic Mineralization

Molecular signaling of the HMGB1/RAGE axis contributes to cholesteatoma pathogenesis

Contact Info

Product

Resources

About