Proinflammatory T cells and IL-17 stimulate osteoblast differentiation

Croes, Michiel; Öner, F. Cumhur; Neerven, Danihel van; Sabir, Ekrem; Kruyt, Moyo C.; Blokhuis, Taco J.; Dhert, Wouter J.A.; Alblas, Jacqueline

doi:10.1016/j.bone.2016.01.010

Cited by 149 publications

(100 citation statements)

References 74 publications

(93 reference statements)

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“…During normal bone fracture healing, bone-promoting growth factors are supported by factors associated with the inflammatory response (Cho et al, 2002;Mountziaris et al, 2011;Rundle et al, 2006). Similarly, we previously observed in vitro that proinflammatory mediators require a second, osteogenic stimulus in order to contribute to osteogenesis Croes et al, 2016). This agrees with the current finding that the co-delivery of these factors creates a potent stimulus for new bone formation.…”

Section: Croes Et Alsupporting

confidence: 91%

“…While several lines of evidence show that TNF-α stimulates the osteoblast differentiation in human MSCs, this effect seems receptor-specific for the TLR agonists Fiedler et al, 2013;Hess et al, 2009). Furthermore, in vitro, pro-inflammatory mediators only promote osteoblast differentiation in the presence of an osteoinductive factor like dexamethasone or BMP-2, suggesting that the commitment of bone progenitor cells to the osteogenic lineage enhances their responsiveness to inflammatory signals Croes et al, 2016;Tomchuck et al, 2008).…”

Section: Croes Et Almentioning

confidence: 99%

“…For example, IL-17-producing T cells contribute to bone healing and MSC osteogenesis (Croes et al, 2016;Nam et al, 2012;Ono et al, 2016), while other proinflammatory T cell subsets can also inhibit bone formation (Liu et al, 2011;Reinke et al, 2013). In a follow-up, a functional assay should elucidate whether lymphocytes are actually involved in the bone formation process in this model.…”

Section: Wwwecmjournalorg M Croes Et Al Local Inflammation Affectsmentioning

confidence: 99%

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Local induction of inflammation affects bone formation

Croes

Kruyt

Loozen

et al. 2017

eCM

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To explore the influence of inflammatory processes on bone formation, we applied a new in vivo screening model. Confined biological pockets were first created in rabbits as a response to implanted bone cement discs. These biomembrane pockets were subsequently used to study the effects of inflammatory stimuli on ectopic bone formation within biphasic calcium phosphate (BCP) constructs loaded with TNF-α, lipopolysaccharide (LPS) or lipoteichoic acid (LTA), all with or without bone morphogenetic protein (BMP)-2. Analysis of bone formation after 12 weeks demonstrated that the inflammatory mediators were not bone-inductive in combination with the BCP alone, but inhibited or enhanced BMP-induced bone formation. LPS was associated with a strong inhibition of bone formation by BMP-2, while LTA and TNF-α showed a positive interaction with BMP-2. Since the biomembrane pockets did not interfere with bone formation and prevented the leakage of pro-inflammatory compounds to the surrounding tissue, the biomembrane model can be used for in vivo approaches to study local inflammation in conjunction with new bone formation. Using this model, it was shown that the modulation of the inflammatory response could be beneficial or detrimental to the subsequent bone formation process. The co-delivery of inflammatory factors and bone-related growth factors should be further explored as a strategy to enhance the bone-forming efficacy of bone substitutes.

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Section: Croes Et Alsupporting

confidence: 91%

Section: Croes Et Almentioning

confidence: 99%

Section: Wwwecmjournalorg M Croes Et Al Local Inflammation Affectsmentioning

confidence: 99%

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Local induction of inflammation affects bone formation

Croes

Kruyt

Loozen

et al. 2017

eCM

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“…IL-17 can inhibit the chondrogenic differentiation of MSCs via the suppression of a key chondrogenesis transcriptional factor, SRY-box 9 (SOX9) and its activator cAMP-dependent protein kinase (PKA) [87]. Additionally, an in vitro work showed that IL-17 also enhances the MSC differentiation into osteoblasts [88]. This all indicates that adaptive lymphocytes can actively participate in the endochondral ossification.…”

Section: Repair Phasementioning

confidence: 99%

The roles of immune cells in bone healing; what we know, do not know and future perspectives

El-Jawhari

Jones

Giannoudis

2016

Injury

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“…IL-17 induces inflammation through the recruitment and activation of immune cells, leading to the release of proinflammatory molecules, such as IL-1 and TNFα, which increase RANKL expression and synergize with RANKL signaling to maximize osteoclast formation [7,31]. However, Croes et al showed that IL-17A and IL-17F exhibit strong osteogenic effects when exposed directly to MSCs [32]. Similar to previous studies [12,33], we found that SOST reduced the expression of collagen, OCN, and OPN, which was accompanied with the increased expression of LPL and PPARγ.…”

Section: Il17mentioning

confidence: 99%

SOST Gene Inhibits Osteogenesis from Adipose-Derived Mesenchymal Stem Cells by Inducing Th17 Cell Differentiation

Chen

Pan

et al. 2018

Cell Physiol Biochem

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Background/Aims: Postmenopausal osteoporosis is considered to be an autoimmune and inflammatory process, and IL-17 plays important roles in the loss of bone mass. Sclerostin (SOST) acts as a negative regulator of bone formation by inhibiting the Wnt signaling pathway. It also is a mediator of the crosstalk between the skeletal and immune systems. However, few studies have examined the role of SOST gene in the differentiation of T helper 17 (Th17) cells. Methods: Adipose-derived stem cells (ADSCs) were isolated and transfected with pcDNA3-SOST or shSOST, and then co-cultured with CD4⁺ T cells isolated from peripheral blood mononuclear cells. The differentiation, adipogenesis, and osteogenesis of Th17 and regulatory T (Treg) cells were examined by western blot, intracellular and intranuclear staining, ELISA, and real-time quantitative PCR in this co-culture model. Results: The SOST gene promoted the secretion of IL-6 and TGF-β in ADSCs. After co-culture of ADSCs with CD4⁺ T cells, the SOST gene increased the number of CD4⁺IL-17⁺ cells and the levels of IL-17 and RORγ. However, the number of CD4⁺CD25⁺Foxp3⁺ cells was decreased, which was accompanied with a reduction of IL-10 and Foxp3 expression. In the meantime, the SOST gene inhibited the expression of COL1, OCN, and OPN, reduced the activity of alkaline phosphatase, and increased the expression of LPL and PPARγ. Furthermore, IL-17 promoted SOST gene-induced adipogenesis and increased the inhibition of osteogenesis. Conclusions: SOST promoted the differentiation of Th17 cells and reduced the differentiation of Treg cells, which exacerbated the SOST gene-induced inhibition of osteogenesis from ADSCs.

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Proinflammatory T cells and IL-17 stimulate osteoblast differentiation

Cited by 149 publications

References 74 publications

Local induction of inflammation affects bone formation

Local induction of inflammation affects bone formation

The roles of immune cells in bone healing; what we know, do not know and future perspectives

SOST Gene Inhibits Osteogenesis from Adipose-Derived Mesenchymal Stem Cells by Inducing Th17 Cell Differentiation

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