Time-of-Flight Secondary Ion Mass Spectrometry-Based Molecular Distribution Distinguishing Healthy and Osteoarthritic Human Cartilage

Cillero‐Pastor, Berta; Eijkel, Gert B.; Kiss, András; Blanco, Francisco J.; Heeren, Ron M. A.

doi:10.1021/ac301853q

Cited by 83 publications

(84 citation statements)

References 41 publications

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“…In a pioneering study conducted by Lipiello and colleagues, elevated FA levels were observed in osteoarthritic articular cartilage, and were positively associated with histological severity (25). More recently, Cillero-Pastor also reported significant FA accumulation in the surface of OA articular cartilage using mass spectrometry (32). Chondrocytes can synthetize and accumulate endogenous lipids and also are able to internalize exogenous FA and store them in lipid droplets (33).…”

Section: Discussionmentioning

confidence: 94%

Palmitate Has Proapoptotic and Proinflammatory Effects on Articular Cartilage and Synergizes With Interleukin‐1

Álvarez-García

Rogers

Smith

et al. 2014

Arthritis & Rheumatology

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Objectives Obesity is a major risk factor for the development of osteoarthritis (OA) that is associated with a state of low-grade inflammation, and increased circulating adipokines and free fatty acids (FFA). The aim of this study was to analyze effects of saturated (palmitate) and monounsaturated (oleate) free fatty acids (FFA) on articular chondrocytes and cartilage. Methods Human articular chondrocytes and fibroblast-like synoviocytes obtained from young healthy donors, and OA chondrocytes from patients undergoing total knee replacement were treated with palmitate or oleate alone or with interleukin 1-β (IL-1β). Cell viability, caspase activation, and gene expression of proinflammatory factors, extracellular matrix proteins, and extracellular proteases were studied. In addition, chondrocyte viability, interleukin-6 (IL-6) production and matrix damage were assessed in bovine and human articular cartilage explants cultured with FFA with or without IL-1β. Results Palmitate, but not oleate, induced caspase activation and cell death in IL-1β-stimulated normal chondrocytes, and upregulated il6 and cox2 expression in chondrocytes and fibroblast-like synoviocytes through toll-like receptor-4 signaling. In cartilage explants, palmitate induced chondrocyte death, IL-6 release and extracellular matrix degradation. Palmitate synergized with IL-1β in stimulating proapoptotic and proinflammatory cellular responses. Pharmacological inhibition of caspases or TLR-4 signaling reduced palmitate and IL-1β-induced cartilage damage. Conclusions Palmitate acts as a pro-inflammatory and catabolic factor that, in synergy with IL-1β, induces chondrocyte apoptosis and articular cartilage breakdown. Collectively, our data suggest that elevated levels of saturated FFA often found in obesity may contribute to OA pathogenesis.

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Section: Discussionmentioning

confidence: 94%

Palmitate Has Proapoptotic and Proinflammatory Effects on Articular Cartilage and Synergizes With Interleukin‐1

Álvarez-García

Rogers

Smith

et al. 2014

Arthritis & Rheumatology

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“…MSI techniques have only recently been implemented in cartilage research. One study employed a time of flight secondary ion mass spectrometry (TOF-SIMS) workflow in order to acquire molecular-specific spatial distribution of lipids in normal and OA cartilage [8]. A further study used MALDI-MSI to identify and study OA specific peptides and proteins in cartilage [9].…”

Section: Introductionmentioning

confidence: 99%

Matrix assisted laser desorption ionization mass spectrometry imaging identifies markers of ageing and osteoarthritic cartilage

et al. 2014

Self Cite

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IntroductionCartilage protein distribution and the changes that occur in cartilage ageing and disease are essential in understanding the process of cartilage ageing and age related diseases such as osteoarthritis. The aim of this study was to investigate the peptide profiles in ageing and osteoarthritic (OA) cartilage sections using matrix assisted laser desorption ionization mass spectrometry imaging (MALDI-MSI).MethodsThe distribution of proteins in young, old and OA equine cartilage was compared following tryptic digestion of cartilage slices and MALDI-MSI undertaken with a MALDI SYNAPT™ HDMS system. Protein identification was undertaken using database searches following multivariate analysis. Peptide intensity differences between young, ageing and OA cartilage were imaged with Biomap software. Analysis of aggrecanase specific cleavage patterns of a crude cartilage proteoglycan extract were used to validate some of the differences in peptide intensity identified. Immunohistochemistry studies validated the differences in protein abundance.ResultsYoung, old and OA equine cartilage was discriminated based on their peptide signature using discriminant analysis. Proteins including aggrecan core protein, fibromodulin, and cartilage oligomeric matrix protein were identified and localised. Fibronectin peptides displayed a stronger intensity in OA cartilage. Age-specific protein markers for collectin-43 and cartilage oligomeric matrix protein were identified. In addition potential fibromodulin and biglycan peptides targeted for degradation in OA were detected.ConclusionsMALDI-MSI provided a novel platform to study cartilage ageing and disease enabling age and disease specific peptides in cartilage to be elucidated and spatially resolved.

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“…[12][13][14] SIMS may be dynamic or static: while dynamic SIMS can analyze only secondary atomic or diatomic ions, static SIMS uses pulsed ions and thereby enables the analysis of organic molecules. [15] In particular, high mass molecules can be analyzed with high sensitivity when cluster ion technology is used.…”

mentioning

confidence: 99%

Single cell lipidomics of SKBR‐3 breast cancer cells by using time‐of‐flight secondary‐ion mass spectrometry

Ide

Waki

Ishizaki

et al. 2014

Surface & Interface Analysis

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and Mitsutoshi Setou a * Breast cancer is the most common cancer among women worldwide. The molecular characterization of breast tumor cells by using single-cell lipidomics remains relatively unexplored. Here, we introduce a time-of-flight secondary-ion mass spectrometry (TOF-SIMS) approach to visualize the lipids in individual breast cancer cells. The SKBR-3 breast cancer cell line was cultured and dispersed into individual cells. After attachment to a substrate, the cells were rinsed with ammonium acetate and were analyzed using TOF-SIMS. The instrument was operated with Bi 3 2+ as the primary ion. The distributions of ions, including positively charged phosphocholine, and negatively charged phosphates and fatty acids, were simultaneously visualized. These ions were distributed predominantly at the cell attachment sites. The signal intensities of fatty acid ions were determined from the mass spectra at the regions-of-interest. The results of fatty acid analyses on breast cancer cells were consistent with those of our previous study in which prominent expression of stearoyl-CoA desaturase 1 in breast cancer cells was demonstrated. Static TOF-SIMS was shown to be an effective method for determining the lipid molecular signature of the plasma membrane of individual breast cancer cells.

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Time-of-Flight Secondary Ion Mass Spectrometry-Based Molecular Distribution Distinguishing Healthy and Osteoarthritic Human Cartilage

Cited by 83 publications

References 41 publications

Palmitate Has Proapoptotic and Proinflammatory Effects on Articular Cartilage and Synergizes With Interleukin‐1

Palmitate Has Proapoptotic and Proinflammatory Effects on Articular Cartilage and Synergizes With Interleukin‐1

Matrix assisted laser desorption ionization mass spectrometry imaging identifies markers of ageing and osteoarthritic cartilage

Single cell lipidomics of SKBR‐3 breast cancer cells by using time‐of‐flight secondary‐ion mass spectrometry

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