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

被引：42

作者：

Huang, Ru-Lin ^{[1
]}

Sun, Yangbai ^{[1
]}

Ho, Chia-Kang ^{[1
]}

Liu, Kai ^{[1
]}

Tang, Qi-Qun ^{[2
]}

Xie, Yun ^{[1
]}

Li, Qingfeng ^{[1
]}

机构：

[1] Shanghai Jiao Tong Univ, Sch Med, Shanghai Peoples Hosp 9, Dept Plast & Reconstruct Surg, 639 Zhizaoju Rd, Shanghai 200011, Peoples R China

[2] Fudan Univ, Shanghai Med Coll, Dept Biochem & Mol Biol, Key Lab Metab & Mol Med,Minist Educ, Shanghai 200032, Peoples R China

来源：

CELL DEATH & DISEASE | 2018年 / 9卷

基金：

中国国家自然科学基金;

关键词：

BONE MORPHOGENETIC PROTEIN-2; STEM-CELLS; RECEPTOR; 1A; REGENERATION; OBESITY; METAANALYSIS; ADIPOCYTE; RHBMP-2; INTERLEUKIN-6; ARTHRODESIS;

D O I：

10.1038/s41419-017-0126-0

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

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.

引用

页数：15

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