Intravenously delivered glucocorticoid liposomes inhibit osteoclast activity and bone erosion in murine antigen-induced arthritis

Hofkens, Wouter; Grevers, Lilyanne C.; Walgreen, Birgitte; Vries, Teun J. de; Leenen, Pieter J. M.; Everts, Vincent; Storm, Gert; Berg, Wim B. van den; Lent, P.L. van

doi:10.1016/j.jconrel.2011.03.001

Cited by 41 publications

(33 citation statements)

References 30 publications

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“…38 Furthermore, a study has been performed to determine the effect of systemic delivery of prednisolone phosphate encapsulated within "stealth" liposomes on bone erosion and osteoclast activity during experimental antigen-induced arthritis. 39 As preclinical evaluation in animals does not necessarily portray human responses, liposome-encapsulated hemoglobin, an artificial oxygen carrier, has been tested in immunodeficient mice reconstituted with human hematopoietic stem cells (cord blood-transfused NOD/SCID/IL-2Rγnull) mice. 40 In a further study, investigators have attempted to improve the specificity and efficiency of gene transfection and make the liposome a better gene transfer vector to the brain by using monoclonal antibody (anti-Lex/stage-specific embryonic antigen-1)-mediated targeting of liposomes.…”

Section: Mts and Liposome-encapsulated Stem Cellsmentioning

confidence: 99%

Clinical significance of metallothioneins in cell therapy and nanomedicine

Sharma¹,

Rais²,

Sandhu³

et al. 2013

IJN

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Mammalian metallothioneins (MTs) are low molecular weight (6-7 kDa) cysteinerich proteins that are specifically induced by metal nanoparticles (NPs). MT induction in cell therapy may provide better protection by serving as antioxidant, anti-inflammatory, antiapoptotic agents, and by augmenting zinc-mediated transcriptional regulation of genes involved in cell proliferation and differentiation. Liposome-encapsulated MT-1 promoter has been used extensively to induce growth hormone or other genes in culture and gene-manipulated animals. MTs are induced as a defensive mechanism in chronic inflammatory conditions including neurodegenerative diseases, cardiovascular diseases, cancer, and infections, hence can serve as early and sensitive biomarkers of environmental safety and effectiveness of newly developed NPs for clinical applications. Microarray analysis has indicated that MTs are significantly induced in drug resistant cancers and during radiation treatment. Nutritional stress and environmental toxins (eg, kainic acid and domoic acid) induce MTs and aggregation of multilamellar electron-dense membrane stacks (Charnoly body) due to mitochondrial degeneration. MTs enhance mitochondrial bioenergetics of reduced nicotinamide adenine dinucleotide-ubiquinone oxidoreductase (complex-1), a rate-limiting enzyme complex involved in the oxidative phosphorylation. Monoamine oxidase-B inhibitors (eg, selegiline) inhibit α-synuclein nitration, implicated in Lewy body formation, and inhibit 1-methyl 4-phenylpyridinium and 3-morpholinosydnonimineinduced apoptosis in cultured human dopaminergic neurons and mesencephalic fetal stem cells. MTs as free radical scavengers inhibit Charnoly body formation and neurodegenerative α-synucleinopathies, hence Charnoly body formation and α-synuclein index may be used as early and sensitive biomarkers to assess NP effectiveness and toxicity to discover better drug delivery and surgical interventions. Furthermore, pharmacological interventions augmenting MTs may facilitate the theranostic potential of NP-labeled cells and other therapeutic agents. These unique characteristics of MTs might be helpful in the synthesis, characterization, and functionalization of emerging NPs for theranostic applications. This report highlights the clinical significance of MTs and their versatility as early, sensitive biomarkers in cell-based therapy and nanomedicine.

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Section: Mts and Liposome-encapsulated Stem Cellsmentioning

confidence: 99%

Clinical significance of metallothioneins in cell therapy and nanomedicine

Sharma¹,

Rais²,

Sandhu³

et al. 2013

IJN

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“…Recently, we found that intravenous liposomal delivery of glucocorticoids greatly improved its potency and a single injection strongly inhibited knee joint inflammation in experimental arthritis [15]–[17]. The strong effect on inhibition of joint inflammation may be due to alteration of the macrophage phenotype within the lining layer.…”

Section: Introductionmentioning

confidence: 99%

Liposomal Targeting of Prednisolone Phosphate to Synovial Lining Macrophages during Experimental Arthritis Inhibits M1 Activation but Does Not Favor M2 Differentiation

et al. 2013

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BackgroundTo determine the effects of liposomal targeting of prednisolone phosphate (Lip-PLP) to synovial lining macrophages on M1 and M2 polarization in vitro and during experimental arthritis.Material and MethodsExperimental arthritis (antigen and immune complex induced) was elicited in mice and prednisolone containing liposomes were given systemically. Synovium was investigated using microarray analysis, RT-PCR and histology. Bone–marrow macrophages were stimulated towards M1 using LPS and IFNγ before treatment by PLP-liposomes. M1 and M2 markers were determined using RT-PCR.ResultsMicroarray analysis of biopsies of inflamed synovium during antigen induced arthritis (AIA) showed an increased M1 signature characterized by upregulation of IL-1β, IL-6 and FcγRI starting from day 1 and lasting up until day 7 after arthritis induction. The M2 signature remained low throughout the 7 day course of arthritis. Treatment of AIA with intravenously delivered Lip-PLP strongly suppressed joint swelling and synovial infiltration whereas colloidal gold containing liposomes exclusively targeted the macrophages within the inflamed synovial intima layer. In vitro studies showed that Lip-PLP phagocytosed by M1 macrophages resulted in a suppression of the M1 phenotype and induction of M2 markers (IL-10, TGF-β, IL-1RII, CD163, CD206 and Ym1). In vivo, Lip-PLP treatment strongly suppressed M1 markers (TNF-α, IL-1β, IL-6, IL-12p40, iNOS, FcγRI, Ciita and CD86) after local M1 activation of lining macrophages with LPS and IFN-γ and during experimental AIA and immune complex arthritis (ICA). In contrast, M2 markers were not significantly upregulated in antigen-induced arthritis and down regulated in immune complex arthritis.ConclusionThis study clearly shows that systemic treatment with PLP-liposomes selectively targets synovial lining macrophages and inhibits M1 activation. In contrast to in vitro findings, PLP-liposomes do not cause a shift of synovial lining macrophages towards M2.

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“…Bone erosion in RA is primarily the result of activated osteoclasts that express enzymes related to bone resorption, such as MMP9, cathepsin K, and TRAP [11], [42]. Figure 6 shows the distribution of cathepsin K immunoreactivity in the ankle joint in the naïve (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…TNF-α is a cytokine produced by macrophages that also plays an important role in RA joint destruction and may mediate MMP-9 and cathepsin K expression in RA by upregulating the transcription factor c-Fos/AP-1 [10], [11]. MMP-9 and cathepsin K in turn play important roles in osteoclastogenesis and osteoclastic activity [38], [40], [44] and are expressed by leukocytes, synovial fibroblasts, chondrocytes, and osteoclasts [39], [40], [42], [43], [46], [47]. Our immunohistochemical analyses revealed AIA-induced MMP-9 and cathepsin K expression in synovial tissue, cartilage, and bone marrow (Fig.…”

Section: Discussionmentioning

confidence: 99%

A Soft Coral-Derived Compound, 11-epi-Sinulariolide Acetate Suppresses Inflammatory Response and Bone Destruction in Adjuvant-Induced Arthritis

et al. 2013

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In recent years, a significant number of metabolites with potent anti-inflammatory properties have been discovered from marine organisms, and several of these compounds are now under clinical trials. In the present study, we isolated 11-epi-sinulariolide acetate (Ya-s11), a cembrane-type compound with anti-inflammatory effects, from the Formosa soft coral Sinularia querciformis. Preliminary screening revealed that Ya-s11 significantly inhibited the expression of the proinflammatory proteins induced nitric oxide synthase and cyclooxygenase-2 in lipopolysaccharide-stimulated murine macrophages. We also examined the therapeutic effects of Ya-s11 on adjuvant-induced arthritis (AIA) in female Lewis rats, which demonstrate features similar to human rheumatoid arthritis (RA). Animal experiments revealed that Ya-s11 (subcutaneously 9 mg/kg once every 2 days from day 7 to day 28 postimmunization) significantly inhibited AIA characteristics. Moreover, Ya-s11 also attenuated protein expression of cathepsin K, matrix metalloproteinases-9 (MMP-9), tartrate-resistant acid phosphatase (TRAP), and tumor necrosis factor-α (TNF-α) in ankle tissues of AIA-rats. Based on its attenuation of the expression of proinflammatory proteins and disease progression in AIA rats, the marine-derived compound Ya-s11 may serve as a useful therapeutic agent for the treatment of RA.

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Intravenously delivered glucocorticoid liposomes inhibit osteoclast activity and bone erosion in murine antigen-induced arthritis

Cited by 41 publications

References 30 publications

Clinical significance of metallothioneins in cell therapy and nanomedicine

Clinical significance of metallothioneins in cell therapy and nanomedicine

Liposomal Targeting of Prednisolone Phosphate to Synovial Lining Macrophages during Experimental Arthritis Inhibits M1 Activation but Does Not Favor M2 Differentiation

A Soft Coral-Derived Compound, 11-epi-Sinulariolide Acetate Suppresses Inflammatory Response and Bone Destruction in Adjuvant-Induced Arthritis

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