Composite scaffolds of nano-hydroxyapatite and silk fibroin enhance mesenchymal stem cell-based bone regeneration via the interleukin 1 alpha autocrine/paracrine signaling loop.
Composite scaffolds of nano-hydroxyapatite (nHAp) and silk fibroin (SF) have been reported to promote bone regeneration mainly through signaling pathways associated with cell-biomaterial interaction. However, it is unclear whether soluble factors also play a role in osteoinduction with nHAp-SF. In this study, we confirmed the biocompatibility and superior osteoinductivity of nHAp-SF scaffolds versus SF scaffolds both in vitro and on a calvarial defect model in vivo. This was followed by further analysis with microarray assay. The cDNA microarray results identified 247 differentially expressed genes in bone marrow mesenchymal stem cells (BMSCs) cultured on SF-nHAp scaffolds versus SF scaffolds. The greatest disparity in gene expression levels were observed with Il1α and Ilr2. Real-time PCR assay validated the results. The addition of IL-1α into cultures of BMSCs with SF significantly increased both Bmp2 and Ilr2 expression. However, with BMSCs alone, the Il1r2 expression increased substantially, whereas Bmp2 expression exhibited a decrease rather than increase. These data suggested that nHAp may exert osteoinductive effects on BMSCs via the secretion of IL-1α in an autocrine/paracrine fashion, and IL-1α activity could be regulated through the synthesis of IL1R2 by BMSCs upon interaction with nHAp. These results complemented our understanding of the underlying mechanisms of biomaterial osteoinductivity.
Centre for Stem Cell and Tissue Engineering, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, 310058, PR China; Zhejiang Provincial Key Laboratory of Tissue Engineering and Regenerative Medicine, Hangzhou, 310058, PR China.
Hua
H
Liu
Centre for Stem Cell and Tissue Engineering, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, 310058, PR China; Zhejiang Provincial Key Laboratory of Tissue Engineering and Regenerative Medicine, Hangzhou, 310058, PR China.
Guo Wei
GW
Xu
Centre for Stem Cell and Tissue Engineering, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, 310058, PR China; Zhejiang Provincial Key Laboratory of Tissue Engineering and Regenerative Medicine, Hangzhou, 310058, PR China.
Ya Fei
YF
Wang
Centre for Stem Cell and Tissue Engineering, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, 310058, PR China; Zhejiang Provincial Key Laboratory of Tissue Engineering and Regenerative Medicine, Hangzhou, 310058, PR China.
Hong Shi
HS
Zhao
Centre for Stem Cell and Tissue Engineering, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, 310058, PR China; Zhejiang Provincial Key Laboratory of Tissue Engineering and Regenerative Medicine, Hangzhou, 310058, PR China.
Si
S
Xiong
Centre for Stem Cell and Tissue Engineering, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, 310058, PR China; Zhejiang Provincial Key Laboratory of Tissue Engineering and Regenerative Medicine, Hangzhou, 310058, PR China.
Yan
Y
Wu
Department of Biosystems Science & Engineering, ETH-Zurich, Mattenstrasse 26, Basel, CH-4058, Switzerland.
Boon Chin
BC
Heng
Centre for Stem Cell and Tissue Engineering, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, 310058, PR China; Zhejiang Provincial Key Laboratory of Tissue Engineering and Regenerative Medicine, Hangzhou, 310058, PR China.
Cheng Rui
CR
An
Institute of Otology, Department of Otolaryngology-Head and Neck Surgery, Second Xiangya Hospital of Central South University, Changsha, Hunan, 410011, PR China. Electronic address: z1g2h3@hotmail.com.
Gang Hua
GH
Zhu
Institute of Otology, Department of Otolaryngology-Head and Neck Surgery, Second Xiangya Hospital of Central South University, Changsha, Hunan, 410011, PR China. Electronic address: dhuaxie@163.com.
Ding Hua
DH
Xie
D000818:Animals; D019898:Autocrine Communication / Q000187:drug effects*; D001672:Biocompatible Materials / Q000494:pharmacology; D001854:Bone Marrow Cells / Q000166:cytology; D055396:Bone Morphogenetic Protein 2 / Q000378:metabolism; D001861:Bone Regeneration / Q000187:drug effects*; D002454:Cell Differentiation / Q000187:drug effects; D048430:Cell Shape / Q000187:drug effects; D016000:Cluster Analysis; D004195:Disease Models, Animal; D017886:Durapatite / Q000494:pharmacology*; D005260:Female; D005349:Fibroins / Q000494:pharmacology*; D053582:Interleukin-1alpha / Q000378:metabolism*; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000648:ultrastructure; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D010012:Osteogenesis / Q000187:drug effects; D019899:Paracrine Communication / Q000187:drug effects*; D017207:Rats, Sprague-Dawley; D053574:Receptors, Interleukin-1 Type II / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D012886:Skull / Q000187:drug effects / Q000473:pathology; D054457:Tissue Scaffolds / Q000737:chemistry*
D001672:Biocompatible Materials; D055396:Bone Morphogenetic Protein 2; D053582:Interleukin-1alpha; D053574:Receptors, Interleukin-1 Type II; D005349:Fibroins; D017886:Durapatite
Bone regeneration; Hydroxyapatite; Interleukin; Osteogenesis; Silk; Stem cell