Synergy between IL-6 and soluble IL-6 receptor enhances bone morphogenetic protein-2/absorbable collagen sponge-induced bone regeneration via regulation of BMPRIA distribution and degradation

Huang, Ru‐Lin; Chen, Gang; Wang, Wenjin; Herller, Tanja; Xie, Yun; Gu, Bin; Li, Qingfeng

doi:10.1016/j.biomaterials.2015.07.047

Cited by 28 publications

(20 citation statements)

References 42 publications

(33 reference statements)

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“…Written informed consent was obtained from all patients. The hBMSCs were established as previously described 23 , 31 . The cells were cultured in Dulbecco’s modified Eagle’s medium (DMEM) supplemented with 10% fetal bovine serum (FBS; Gibco, CA, USA).…”

Section: Methodsmentioning

confidence: 99%

“…Among the elevated inflammatory mediators, tumor necrosis factor (TNF)-α and interleukin (IL)-1β play an inhibitory role in the rhBMP-2-induced osteogenic differentiation of BMSCs 11 , 21 , 22 . However, IL-6 seems to be an exception, showing a synergetic effect with rhBMP-2 to enhance bone regeneration in an animal model 23 . IL-6 is a highly pleiotropic cytokine, and its effects on bone and adipose metabolism are controversial and unresolved 24 .…”

Section: Introductionmentioning

confidence: 97%

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IL-6 potentiates BMP-2-induced osteogenesis and adipogenesis via two different BMPR1A-mediated pathways

Huang

Sun

et al. 2018

Cell Death Dis

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Recombinant human bone morphogenetic protein-2 (rhBMP-2) is widely used in the clinic for bone defect reconstruction because of its powerful osteoinductive capacity. However, commercially available rhBMP-2 requires a high concentration in the clinical setting for consistent bone formation. A high dose of rhBMP-2 induces a promising bone formation yield but also leads to inflammation-related events, deteriorated bone quality, and fatty tissue formation. We hypothesize that the seemingly contradictory phenomenon of coformation of new bone and excessive adipose tissue in rhBMP-2-induced bone voids may be associated with interleukin-6 (IL-6), which is significantly elevated after application of rhBMP-2/absorbable collagen sponge (rhBMP-2/ACS). Here, we show that IL-6 injection enhances new bone regeneration and induces excessive adipose tissue formation in an rhBMP-2/ACS-induced ectopic bone formation model in rats. In vitro data further show that IL-6 and its soluble receptor sIL-6R synergistically augment rhBMP-2-induced osteogenic and adipogenic differentiation of human BMSCs (hBMSCs) by promoting cell surface translocation of BMPR1A and then amplifying BMPR1A-mediated BMP/Smad and p38 MAPK pathways, respectively. Our study suggests elevated IL-6 may be responsible for coformation of new bone and excessive adipose tissue in rhBMP-2-induced bone voids.

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Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 97%

IL-6 potentiates BMP-2-induced osteogenesis and adipogenesis via two different BMPR1A-mediated pathways

Huang

Sun

et al. 2018

Cell Death Dis

Self Cite

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“…The subcutaneous pocket is the simplest model of all IVB strategies for bone graft prefabrication and has been widely used in ectopic bone formation models (Huang et al, 2014, Huang et al, 2015). Only reports that aimed to regenerate bone grafts following the IVB principle are included in this review.…”

Section: Bone Graft Prefabrication Following the Ivb Principle: Basicmentioning

confidence: 99%

Bone Graft Prefabrication Following the In Vivo Bioreactor Principle

Huang

Kobayashi

et al. 2016

EBioMedicine

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Large bone defect treatment represents a great challenge due to the difficulty of functional and esthetic reconstruction. Tissue-engineered bone grafts created by in vitro manipulation of bioscaffolds, seed cells, and growth factors have been considered potential treatments for bone defect reconstruction. However, a significant gap remains between experimental successes and clinical translation. An emerging strategy for bridging this gap is using the in vivo bioreactor principle and flap prefabrication techniques. This principle focuses on using the body as a bioreactor to cultivate the traditional triad (bioscaffolds, seed cells, and growth factors) and leveraging the body's self-regenerative capacity to regenerate new tissue. Additionally, flap prefabrication techniques allow the regenerated bone grafts to be transferred as prefabricated bone flaps for bone defect reconstruction. Such a strategy has been used successfully for reconstructing critical-sized bone defects in animal models and humans. Here, we highlight this concept and provide some perspective on how to translate current knowledge into clinical practice.

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“…In addition, other growth factors have shown a similar ability to manipulate the BMPR distribution. Synergistic effects of IL‐6 and BMP‐2 were observed in bone regeneration due to the distribution and degradation of BMPR‐IA regulated by IL‐6, which suggests an interference in BMP signaling . Thus, the interaction between biomaterials and BMPRs localization is mainly mediated by integrins or other growth factors carried by biomaterials, which provides a promising strategy for modulating the bioactivity of BMPs.…”

Section: Biomaterials Act As Enhancers Of Growth Factors In Bone Regementioning

confidence: 99%

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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Synergy between IL-6 and soluble IL-6 receptor enhances bone morphogenetic protein-2/absorbable collagen sponge-induced bone regeneration via regulation of BMPRIA distribution and degradation

Cited by 28 publications

References 42 publications

IL-6 potentiates BMP-2-induced osteogenesis and adipogenesis via two different BMPR1A-mediated pathways

IL-6 potentiates BMP-2-induced osteogenesis and adipogenesis via two different BMPR1A-mediated pathways

Bone Graft Prefabrication Following the In Vivo Bioreactor Principle

Biomaterials Act as Enhancers of Growth Factors in Bone Regeneration

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