Chondroprotective effect of zinc oxide nanoparticles in conjunction with hypoxia on bovine cartilage-matrix synthesis.
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 environment.
Faculty of Engineering, Department of Biomedical Engineering, University of Malaya, Kuala Lumpur, 50603, Kuala Lumpur, Malaysia.|Department of Biomedical Technology, College of Applied Medical Sciences, King Saud University, Riyadh, Kingdom of Saudi Arabia.
Eraj Humayun
EH
Mirza
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.
Chong
C
Pan-Pan
Faculty of Engineering, Department of Biomedical Engineering, University of Malaya, Kuala Lumpur, 50603, Kuala Lumpur, Malaysia.
Wan Mohd Azhar Bin
WM
Wan Ibrahim
Faculty of Engineering, Department of Biomedical Engineering, University of Malaya, Kuala Lumpur, 50603, Kuala Lumpur, Malaysia.
Ivan
I
Djordjevic
Faculty of Engineering, Department of Biomedical Engineering, University of Malaya, Kuala Lumpur, 50603, Kuala Lumpur, Malaysia.
Belinda
B
Pingguan-Murphy
D000818:Animals; D002358:Cartilage, Articular / Q000187:drug effects / Q000378:metabolism*; D002417:Cattle; D015687:Cell Hypoxia / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D019902:Chondrocytes / Q000166:cytology* / Q000187:drug effects / Q000648:ultrastructure; D019610:Cytoprotection / Q000187:drug effects*; D004247:DNA / Q000378:metabolism; D005109:Extracellular Matrix / Q000187:drug effects / Q000378:metabolism*; D005453:Fluorescence; D005786:Gene Expression Regulation / Q000187:drug effects; D053758:Nanoparticles / Q000737:chemistry*; D011509:Proteoglycans / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D054457:Tissue Scaffolds / Q000737:chemistry; D015034:Zinc Oxide / Q000494:pharmacology*
D011509:Proteoglycans; D012333:RNA, Messenger; D004247:DNA; D015034:Zinc Oxide
articular cartilage; elastomeric scaffolds; hypoxia; nanocomposite; nanoparticles; zinc oxide