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Int. J. Mol. Sci. 2015, 16(10), 24946-24964; doi:10.3390/ijms161024946

The Osteogenesis Effect and Underlying Mechanisms of Local Delivery of gAPN in Extraction Sockets of Beagle Dogs

1,2,†
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1,2,†
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1,2,†
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3
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1,2
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1,2
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1,2
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2
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4
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1,2,* and 1,2,*
1
2nd Dental Center, Peking University School and Hospital of Stomatology, Beijing 100101, China
2
National Engineering Laboratory for Digital and Material Technology of Stomatology, Peking University School and Hospital of Stomatology, Beijing 100081, China
3
Department of Laboratory Animal Science, Peking University Health Science Center, Beijing 100191, China
4
Department of Polymer Science & Engineering College of Chemistry & Molecular Engineering, Peking University, Beijing 100871, China
These authors contributed equally to this work.
*
Authors to whom correspondence should be addressed.
Academic Editor: Wenbin Deng
Received: 5 August 2015 / Revised: 21 September 2015 / Accepted: 13 October 2015 / Published: 20 October 2015
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Abstract

A plastic and biodegradable bone substitute consists of poly (l-lactic-co-glycolic) acid and 30 wt % β-tricalcium phosphate has been previously fabricated, but its osteogenic capability required further improvement. We investigated the use of globular adiponectin (gAPN) as an anabolic agent for tissue-engineered bone using this scaffold. A qualitative analysis of the bone regeneration process was carried out using μCT and histological analysis 12 weeks after implantation. CBCT (Cone Beam Computed Tomography) superimposition was used to characterise the effect of the different treatments on bone formation. In this study, we also explored adiponectin’s (APN) influence on primary cultured human jaw bone marrow mesenchymal stem cells gene expressions involved in the osteogenesis. We found that composite scaffolds loaded with gAPN or bone morphogenetic protein 2 (BMP2) exhibited significantly increased bone formation and mineralisation following 12 weeks in the extraction sockets of beagle dogs, as well as enhanced expression of osteogenic markers. In vitro investigation revealed that APN also promoted osteoblast differentiation of primary cultured human jaw bone marrow mesenchymal stem cells (h-JBMMSCs), accompanied by increased activity of alkaline phosphatase, greater mineralisation, and production of the osteoblast-differentiated genes osteocalcin, bone sialoprotein and collagen type I, which was reversed by APPL1 siRNA. Therefore, the composite scaffold loaded with APN exhibited superior activity for guided bone regeneration compared with blank control or Bio-Oss® (a commercially available product). The composite scaffold with APN has significant potential for clinical applications in bone tissue engineering. View Full-Text
Keywords: adiponectin; BMP2 (bone morphogenetic protein 2); dental material; mesenchymal stem cells; beagle dog adiponectin; BMP2 (bone morphogenetic protein 2); dental material; mesenchymal stem cells; beagle dog
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MDPI and ACS Style

Hu, H.; Pu, Y.; Lu, S.; Zhang, K.; Guo, Y.; Lu, H.; Li, D.; Li, X.; Li, Z.; Wu, Y.; Tang, Z. The Osteogenesis Effect and Underlying Mechanisms of Local Delivery of gAPN in Extraction Sockets of Beagle Dogs. Int. J. Mol. Sci. 2015, 16, 24946-24964.

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