Chondroprotective effect of zinc oxide nanoparticles in conjunction with hypoxia on bovine cartilage-matrix synthesis Eraj Humayun Mirza,1,2 Chong Pan-Pan,3 Wan Mohd Azhar Bin Wan Ibrahim,1 Ivan Djordjevic,1 Belinda Pingguan-Murphy1 1
Faculty of Engineering, Department of Biomedical Engineering, University of Malaya, Kuala Lumpur 50603, Kuala Lumpur, Malaysia 2 Department of Biomedical Technology, College of Applied Medical Sciences, King Saud University, Riyadh, Kingdom of Saudi Arabia 3 Faculty of Medicine, Department of Orthopaedic Surgery, Tissue Engineering Group (TEG), National Orthopaedic Centre of Excellence for Research and Learning (NOCERAL), University of Malaya, 50603 Kuala Lumpur, Malaysia Received 8 January 2015; revised 1 April 2015; accepted 30 April 2015 Published online 27 May 2015 in Wiley Online Library (wileyonlinelibrary.com). DOI: 10.1002/jbm.a.35495 Abstract: Articular cartilage is a tissue specifically adapted to a specific niche with a low oxygen tension (hypoxia), and the presence of such conditions is a key factor in regulating growth and survival of chondrocytes. Zinc deficiency has been linked to cartilage-related disease, and presence of Zinc is known to provide antibacterial benefits, which makes its inclusion attractive in an in vitro system to reduce infection. Inclusion of 1% zinc oxide nanoparticles (ZnONP) in poly octanediol citrate (POC) polymer cultured in hypoxia has not been well determined. In this study we investigated the effects of ZnONP on chondrocyte proliferation and matrix synthesis cultured under normoxia (21% O2) and hypoxia (5% O2). We report an upregulation of chondrocyte proliferation and sulfated glycosaminoglycan (S-GAG) in hypoxic culture.
Results demonstrate a synergistic effect of oxygen concentration and 1% ZnONP in up-regulation of anabolic gene expression (Type II collagen and aggrecan), and a down regulation of catabolic (MMP-13) gene expression. Furthermore, production of transcription factor hypoxia-inducible factor 1A (HIF-1A) in response to hypoxic condition to regulate chondrocyte survival under hypoxia is not affected by the presence of 1% ZnONP. Presence of 1% ZnONP appears to act to preserve homeostasis of cartilage in its hypoxic enviC 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part A: ronment. V 103A: 3554–3563, 2015.
Key Words: articular cartilage, elastomeric scaffolds, hypoxia, nanocomposite, zinc oxide, nanoparticles
How to cite this article: Humayun Mirza E, Pan-Pan C, Mohd Azhar Bin Wan Ibrahim W, Djordjevic I, Pingguan-Murphy B. 2015. Chondroprotective effect of zinc oxide nanoparticles in conjunction with hypoxia on bovine cartilage-matrix synthesis. J Biomed Mater Res Part A 2015:103A:3554–3563.
INTRODUCTION
The physiological environment of articular cartilage is typically avascular and aneural.1 Moreover, it is well established that the microenvironment of cartilage is hypoxic, with oxygen (O2) tension ranging from
Faculty of Engineering, Department of Biomedical Engineering, University of Malaya, Kuala Lumpur 50603, Kuala Lumpur, Malaysia 2 Department of Biomedical Technology, College of Applied Medical Sciences, King Saud University, Riyadh, Kingdom of Saudi Arabia 3 Faculty of Medicine, Department of Orthopaedic Surgery, Tissue Engineering Group (TEG), National Orthopaedic Centre of Excellence for Research and Learning (NOCERAL), University of Malaya, 50603 Kuala Lumpur, Malaysia Received 8 January 2015; revised 1 April 2015; accepted 30 April 2015 Published online 27 May 2015 in Wiley Online Library (wileyonlinelibrary.com). DOI: 10.1002/jbm.a.35495 Abstract: Articular cartilage is a tissue specifically adapted to a specific niche with a low oxygen tension (hypoxia), and the presence of such conditions is a key factor in regulating growth and survival of chondrocytes. Zinc deficiency has been linked to cartilage-related disease, and presence of Zinc is known to provide antibacterial benefits, which makes its inclusion attractive in an in vitro system to reduce infection. Inclusion of 1% zinc oxide nanoparticles (ZnONP) in poly octanediol citrate (POC) polymer cultured in hypoxia has not been well determined. In this study we investigated the effects of ZnONP on chondrocyte proliferation and matrix synthesis cultured under normoxia (21% O2) and hypoxia (5% O2). We report an upregulation of chondrocyte proliferation and sulfated glycosaminoglycan (S-GAG) in hypoxic culture.
Results demonstrate a synergistic effect of oxygen concentration and 1% ZnONP in up-regulation of anabolic gene expression (Type II collagen and aggrecan), and a down regulation of catabolic (MMP-13) gene expression. Furthermore, production of transcription factor hypoxia-inducible factor 1A (HIF-1A) in response to hypoxic condition to regulate chondrocyte survival under hypoxia is not affected by the presence of 1% ZnONP. Presence of 1% ZnONP appears to act to preserve homeostasis of cartilage in its hypoxic enviC 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part A: ronment. V 103A: 3554–3563, 2015.
Key Words: articular cartilage, elastomeric scaffolds, hypoxia, nanocomposite, zinc oxide, nanoparticles
How to cite this article: Humayun Mirza E, Pan-Pan C, Mohd Azhar Bin Wan Ibrahim W, Djordjevic I, Pingguan-Murphy B. 2015. Chondroprotective effect of zinc oxide nanoparticles in conjunction with hypoxia on bovine cartilage-matrix synthesis. J Biomed Mater Res Part A 2015:103A:3554–3563.
INTRODUCTION
The physiological environment of articular cartilage is typically avascular and aneural.1 Moreover, it is well established that the microenvironment of cartilage is hypoxic, with oxygen (O2) tension ranging from
