Curcumin increases rat mesenchymal stem cell osteoblast differentiation but inhibits adipocyte differentiation

Gu, Qianqun; Cai, Yan; Huang, Chen; Shi, Qin; Yang, Huilin

doi:10.4103/0973-1296.99285

Cited by 83 publications

(48 citation statements)

References 34 publications

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“…PPAR-γ, however, was not significantly downregulated at the same curcumin concentration. The results confirmed literature reports that free curcumin within a concentration range of 5-10 μM in the medium inhibited hBMSCs adipogenesis [35]. Accumulation of lipid droplets due to adipocyte maturation was then examined by oil red O staining.…”

Section: Resultssupporting

confidence: 86%

“…Thus, film-associated curcumin accelerated hBMSC adipogenesis. Curcumin may integrate into the lipid bilayer of cell membranes, change membrane properties or interact with cell membrane proteins, further triggering intracellular signaling pathways, such as MAPK and Wnt/β-catenin pathways that are important for the modulation of osteogenic and adipogenic differentiation of MSCs [35]. …”

Section: Resultsmentioning

confidence: 99%

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Curcumin-functionalized silk materials for enhancing adipogenic differentiation of bone marrow-derived human mesenchymal stem cells

Luo

Zheng

et al. 2015

Acta Biomaterialia

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Curcumin, a natural phenolic compound derived from the plant Curcuma longa, was physically entrapped and stabilized in silk hydrogel films and its influence on human bone marrow-derived mesenchymal stem cells (hBMSCs) was assessed related to adipogenic differentiation. The presence of curcumin significantly reduced silk gelation time and changed the porous morphology of gel matrix, but did not change the formation of silk beta-sheet structure. Based on spectrofluorimetric analysis, curcumin likely interacted with hydrophobic residues in silk, interacting with the beta-sheet domains formed in the hydrogels. The antioxidant activity of silk film-associated curcumin remained functional over at least one month in both the dry and hydrated state. Negligible curcumin was released from silk hydrogel films over 48 hours incubation in aqueous solution. For hBMSCs cultured on silk films containing more than 0.25 mg/mL curcumin, cell proliferation was inhibited while adipogenesis was significantly promoted based on transcripts as well as oil red O staining. When hBMSCs were cultured in media containing free curcumin, both proliferation and adipogenesis of hBMSCs were inhibited when curcumin concentrations exceeded 5 μM, which is more than 1,000-times higher than the level of curcumin released from the films in aqueous solution. Thus, silk film-associated curcumin exhibited different effects on hBMSC proliferation and differentiation when compared to curcumin in solution.

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Section: Resultssupporting

confidence: 86%

Section: Resultsmentioning

confidence: 99%

Curcumin-functionalized silk materials for enhancing adipogenic differentiation of bone marrow-derived human mesenchymal stem cells

Luo

Zheng

et al. 2015

Acta Biomaterialia

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“…Curcumin is derived from turmeric and has been shown to inhibit NF-κB as well as downregulating cyclooxygenase-2, nitric oxide synthase, and matrix metalloproteinase-9 [51]. It has also been reported that curcumin can promote osteogenesis and inhibit adipogenesis in rat MSCs, although the mechanism for this is unclear [52]. A pathway of particular interest is the p38 MAPK pathway, and it has been demonstrated that alterations in differentiation potential of human MSCs by modification of the actin cytoskeleton are associated with changes in the levels of phosphorylated p38 MAPK [53].…”

Section: Discussionmentioning

confidence: 99%

TNFα and IL-1β influence the differentiation and migration of murine MSCs independently of the NF-κB pathway

et al. 2014

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IntroductionMesenchymal stem cells (MSCs) have the ability to repair and regenerate tissue, home to sites of inflammation, and evade the host immune system. As such, they represent an attractive therapy for the treatment of autoimmune inflammatory diseases. However, results from in vivo murine studies in inflammatory arthritis have been conflicting, and this may be due to the genetic background of the MSCs used. It is known that the inflammatory milieu may influence properties of MSCs and that, in the case of human bone marrow-derived MSCs, this may be mediated by the nuclear factor-kappa-B (NF-κB) pathway. We sought to determine whether pro-inflammatory cytokines altered the differentiation and migration capacity of murine MSCs from different mouse strains and whether this was mediated by NF-κB.MethodsThe differentiation and migration of FVB and BALB/c MSCs were carried out in the presence of varying concentrations of tumor necrosis factor-alpha (TNFα) and interleukin (IL)-1β, and the NF-κB pathway was inhibited in one of two ways: either by transduction of MSCs with an adenoviral vector expressing a super-repressor of NF-κB or by the addition of curcumin to culture media.ResultsBoth BALB/c and FVB MSCs were sensitive to the effect of pro-inflammatory cytokines in vitro. TNFα and IL-1β suppressed BALB/c osteogenesis and adipogenesis and FVB osteogenesis. The migration of both cell types toward media containing fetal bovine serum was augmented by pre-stimulation with either cytokine. In neither cell type were the cytokine effects reversed by abrogation of the NF-κB pathway.ConclusionsThese data show that murine MSCs from different genetic backgrounds may be influenced by an inflammatory milieu in a manner that is not mediated by NF-κB, as is the case for human MSCs. This is not mediated by NF-κB. These findings are important and should influence how in vivo trials of murine MSCs are interpreted and the future development of pre-clinical studies in inflammatory diseases.Electronic supplementary materialThe online version of this article (doi:10.1186/scrt492) contains supplementary material, which is available to authorized users.

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“…With respect to osteotropic effects, curcumin exerts an inhibitory effect of bone resorption via enhanced osteoclast apoptosis (Ozaki et al, 2000), and it stimulates osteoblast differentiation (Gu et al, 2012). Early exposure of a multi-functional drug controllably released from the proposed CS composites could enhance bioactivity of the materials.…”

Section: Discussionmentioning

confidence: 99%

Bioerodible calcium sulfate/poly(β-amino ester) hydrogel composites

Orellana

Thomas

Dziubla

et al. 2013

Journal of the Mechanical Behavior of Biomedical Materials

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The capacity to quickly regenerate or augment bone lost as a result of resorption is crucial to ensure suitable application of prosthetics for restoring masticatory function. Calcium sulfate hemihydrate (CS)-based bone graft substitute composites containing poly(β-amino ester) (PBAE) biodegradable hydrogel particles were developed to act as a ‘tenting’ barrier to soft tissue infiltration, potentially providing adequate space to enable vertical bone regeneration. CS has long been recognized as an osteoconductive biomaterial with an excellent reputation as a biocompatible substance. Composite samples were fabricated with varying amounts (1 or 10 wt%) and sizes (53–150 or 150–250 µm) of gel particles embedded in CS. The swelling and degradation rates of PBAE gels alone were rapid, resulting in complete degradation in less than 24 hours, an important characteristic to aid in controlled release of drug. MicroCT images revealed a homogeneous distribution of gel particles within the CS matrix. All CS samples degraded via surface erosion, with the amount of gel particles (i.e., 10 wt% gel particles) having only a small, but significant, effect on the dissolution rate (4% vs. 5% per day). Compression testing determined that the amount, but not the size, of gel particles had a significant effect on the overall strength of the composites. As much as a 75% drop in strength was seen with a 10 wt% loading of particles. A pilot study using PBAE particles loaded with the multipotential drug curcumin demonstrated sustained release of drug from CS composites. By adjusting the amount and/or size of the biodegradable gel particles embedded in CS, mechanical strength and degradation rates of the composites, as well as the drug release kinetics, can be tuned to provide sufficient, multi-functional ‘space-making’ bone grafting substitutes.

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Curcumin increases rat mesenchymal stem cell osteoblast differentiation but inhibits adipocyte differentiation

Cited by 83 publications

References 34 publications

Curcumin-functionalized silk materials for enhancing adipogenic differentiation of bone marrow-derived human mesenchymal stem cells

Curcumin-functionalized silk materials for enhancing adipogenic differentiation of bone marrow-derived human mesenchymal stem cells

TNFα and IL-1β influence the differentiation and migration of murine MSCs independently of the NF-κB pathway

Bioerodible calcium sulfate/poly(β-amino ester) hydrogel composites

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