TNF-α and IL-1β inhibit RUNX2 and collagen expression but increase alkaline phosphatase activity and mineralization in human mesenchymal stem cells

Ding, Jie; Ghali, Olfa; Lencel, P.; Broux, Odile; Chauveau, Christophe; Devedjian, Jean-Christophe; Hardouin, Pierre; Magne, David

doi:10.1016/j.lfs.2009.01.013

Cited by 192 publications

(169 citation statements)

References 43 publications

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“…For the determination of TNAP activity by the method of Lowry [2], cells cultured in 6-well plates were harvested in 0.2% Nonidet P-40 and disrupted by sonication. Calcium deposition was determined using 2% Alizarin Red staining at pH 4.2 for 2 min, after quantification by extracting the stain with 100 mM cetylpyridinium chloride for 2 h [30].…”

Section: Methodsmentioning

confidence: 99%

“…MSCs were obtained from two healthy donors [a 34-year old female and a 36-year-old male] (Lonza, Walkersville, USA) and also in MSCs obtained from one patient with Legg-Perthes-Calve disease [2]. MSCs were seeded at a density of 5000 cells per cm 2 and cultured in DMEM containing 100 U/ml penicillin, 100 lg/ml streptomycin, and 2 mM L-glutamine (Eurobio, Les Ulis, France).…”

Section: Cell Culturesmentioning

confidence: 99%

“…MSCs were seeded at a density of 5000 cells per cm 2 and cultured in DMEM containing 100 U/ml penicillin, 100 lg/ml streptomycin, and 2 mM L-glutamine (Eurobio, Les Ulis, France). Cells were maintained at 37°C in a humidified atmosphere with 5% CO 2 in air.…”

Section: Cell Culturesmentioning

confidence: 99%

“…Cells were maintained at 37°C in a humidified atmosphere with 5% CO 2 in air. Osteoblast differentiation was induced at confluence with 10 À8 M 1,25(OH) 2 VD3, 50 lM vitamin C and 10 mM b-GP (Sigma-Aldrich, St Quentin Fallavier, France) [2].…”

Section: Cell Culturesmentioning

confidence: 99%

“…In rheumatoid arthritis (RA) for instance, TNF-a and interleukin (IL)-1b reduce bone formation [1]. TNF-a and IL-1b block expression of the osteoblast master transcription factor RUNX2 and trigger its degradation, provoking a decrease in collagen expression and consequently of bone formation [2,3]. On the opposite, excessive ossification is a hallmark of ankylosing spondylitis (AS), an inflammatory disease that affects the axial skeleton and the peripheral joints [4].…”

Section: Introductionmentioning

confidence: 99%

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Autocrine stimulation of osteoblast activity by Wnt5a in response to TNF-α in human mesenchymal stem cells

Briolay

Lencel²,

Bessueille

et al. 2013

Biochemical and Biophysical Research Communications

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a b s t r a c tAlthough anti-tumor necrosis factor (TNF)-a treatments efficiently block inflammation in ankylosing spondylitis (AS), they are inefficient to prevent excessive bone formation. In AS, ossification seems more prone to develop in sites where inflammation has resolved following anti-TNF therapy, suggesting that TNF-a indirectly stimulates ossification. In this context, our objectives were to determine and compare the involvement of Wnt proteins, which are potent growth factors of bone formation, in the effects of TNF-a on osteoblast function. In human mesenchymal stem cells (MSCs), TNF-a significantly increased the levels of Wnt10b and Wnt5a. Associated with this effect, TNF-a stimulated tissue-non specific alkaline phosphatase (TNAP) and mineralization. This effect was mimicked by activation of the canonical bcatenin pathway with either anti-Dkk1 antibodies, lithium chloride (LiCl) or SB216763. TNF-a reduced, and activation of b-catenin had little effect on expression of osteocalcin, a late marker of osteoblast differentiation. Surprisingly, TNF-a failed to stabilize b-catenin and Dkk1 did not inhibit TNF-a effects. In fact, Dkk1 expression was also enhanced in response to TNF-a, perhaps explaining why canonical signaling by Wnt10b was not activated by TNF-a. However, we found that Wnt5a also stimulated TNAP in MSCs cultured in osteogenic conditions, and increased the levels of inflammatory markers such as COX-2. Interestingly, treatment with anti-Wnt5a antibodies reduced endogenous TNAP expression and activity. Collectively, these data suggest that increased levels of Dkk1 may blunt the autocrine effects of Wnt10b, but not that of Wnt5a, acting through non-canonical signaling. Thus, Wnt5a may be potentially involved in the effects of inflammation on bone formation.

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Section: Methodsmentioning

confidence: 99%

Section: Cell Culturesmentioning

confidence: 99%

Section: Cell Culturesmentioning

confidence: 99%

Section: Cell Culturesmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Autocrine stimulation of osteoblast activity by Wnt5a in response to TNF-α in human mesenchymal stem cells

Briolay

Lencel²,

Bessueille

et al. 2013

Biochemical and Biophysical Research Communications

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Biomaterials Act as Enhancers of Growth Factors in Bone Regeneration

Chen

Wang

Liu

2016

Adv Funct Materials

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Inspired by the physiological events of the “wound healing cascade”, the integration of biomaterials and growth factors is generally accepted as an emerging and powerful strategy for bone regenerative therapy. As a type of biological mediator, growth factors play a key role in functional bone regeneration. In this review, recent progress in the enhancement of bone‐related growth factors via a biomaterial strategy will be discussed. Two main reinforcing mechanisms, temporal regulation and efficacy manipulation, are described in detail, highlighting the potential capability of biomaterials to harness the interactions between growth factors and specific cells. The effects of biomaterials for promoting bone formation via growth factor‐mediated osteogenesis are further elucidated. Finally, an outlook of the prospects in terms of superior communication among growth factors, cells, and biomaterials in the microenvironment is presented, which might provide new directions for the design of medical devices for bone regeneration.

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3D Bioprinted Silk‐Based In Vitro Osteochondral Model for Osteoarthritis Therapeutics

Singh

Moses

Bandyopadhyay

et al. 2022

Adv Healthcare Materials

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3D bioprinting of osteochondral tissue offers unique opportunities for enabling precise pharmacological interventions in osteoarthritis (OA). The current study investigates the screening potential of anti-inflammatory drugs using bioprinted inflamed human osteochondral units. The biomimetic hierarchical geometry is bioprinted using silk-based bioinks encapsulating pre-differentiated stem cells, creating an in vitro model. Inflammation is stimulated in the model, using tumor necrosis factor-alpha and Interleukin-1 beta pro-inflammatory cytokines. The resultant degeneration, akin to OA, is flagged by key markers like sulfated glycosaminoglycan, collagen, alkaline phosphatase, and downregulation of osteochondral transcript levels. In the next step, the screening of anti-inflammatory drugs is validated using celecoxib and rhein. Consequently, in the inflamed constructs, the initial upregulation of the key inflammatory mediators (nitric oxide, Prostaglandin E2), is subsequently downregulated, post-drug treatment. In addition, catabolic markers (matrix metalloproteinases and aggrecanase-1), indicative of hypertrophic and apoptosing chondrocytes, are significantly downregulated in the treatment groups; while the transcript and protein levels required for osteochondral health are attenuated. Therefore, the in vitro model mimicks the inflammation in the early stages of OA, and corroborates a potential high-throughput platform for screening novel anti-inflammatory drugs in OA therapeutics.

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TNF-α and IL-1β inhibit RUNX2 and collagen expression but increase alkaline phosphatase activity and mineralization in human mesenchymal stem cells

Cited by 192 publications

References 43 publications

Autocrine stimulation of osteoblast activity by Wnt5a in response to TNF-α in human mesenchymal stem cells

Autocrine stimulation of osteoblast activity by Wnt5a in response to TNF-α in human mesenchymal stem cells

Biomaterials Act as Enhancers of Growth Factors in Bone Regeneration

3D Bioprinted Silk‐Based In Vitro Osteochondral Model for Osteoarthritis Therapeutics

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