Nano-hydroxyapatite modulates osteoblast lineage commitment by stimulation of DNA methylation and regulation of gene expression |
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| Affiliation: | 1. The Atlanta Department of Veterans Affairs Medical Center, Decatur, GA 30033, United States;2. Department of Medicine, Division of Endocrinology Metabolism and Lipids, Emory University, Atlanta, GA 30322, United States;3. Department of Materials Science and Engineering, Seoul National University, Seoul 151-744, Republic of Korea;4. The Winship Cancer Institute, Emory University School of Medicine, Atlanta, GA 30322, United States;1. National and Local United Engineering Laboratory of Tissue Engineering, Department of Orthopedics, Southwest Hospital, the Third Military Medical University, Chongqing, China;2. Laboratory of Tissue Engineering in Chongqing City, Chongqing, 400038, China;3. Center of Regenerative and Reconstructive Engineering Technology in Chongqing City, Chongqing, 400038, China;4. Department of Orthopaedics, No. 519 Hospital of PLA, Xichang, 615000, China;1. Department of Orthopedics, the Affiliated Taizhou Hospital, Wenzhou Medical University, Linhai City, 317000, China;2. Department of Pharmacology, Zhejiang University School of Medicine, Hangzhou, 310058, China;1. Nemours Center for Childhood Cancer Research, Alfred I. duPont Hospital for Children, Wilmington, DE 19803, United States;2. Department of Biological Sciences, University of Delaware, Wilmington, DE 19716, United States;1. Department of Magnetic Resonance Imaging, Zhongnan Hospital, Wuhan University, No. 185 Donghu Road, Wuhan 430071, PR China;2. Department of Interventional Radiology, Inner Mongolia Autonomous Region People''s Hospital, Hohhot, Inner Mongolia 010017, PR China;1. Institute of Polymer Science and Engineering, National Taiwan University, Taipei, Taiwan;2. Division of Plastic and Reconstructive Surgery, Department of Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan;3. Department of Orthopedics, Shuang Ho Hospital, Taipei Medical University, Taipei, Taiwan;4. Research Center for Developmental Biology and Regenerative Medicine, National Taiwan University, Taipei, Taiwan |
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| Abstract: | Hydroxyapatite (HA) is the primary structural component of the skeleton and dentition. Under biological conditions, HA does not occur spontaneously and therefore must be actively synthesized by mineralizing cells such as osteoblasts. The mechanism(s) by which HA is actively synthesized by cells and deposited to create a mineralized matrix are not fully understood and the consequences of mineralization on cell function are even less well understood. HA can be chemically synthesized (HAp) and is therefore currently being investigated as a promising therapeutic biomaterial for use as a functional scaffold and implant coating for skeletal repair and dental applications. Here we investigated the biological effects of nano-HAp (10 × 100 nm) on the lineage commitment and differentiation of bone forming osteoblasts. Exposure of early stage differentiating osteoblasts resulted in dramatic and sustained changes in gene expression, both increased and decreased, whereas later stage osteoblasts were much less responsive. Analysis of the promoter region one of the most responsive genes, alkaline phosphatase, identified the stimulation of DNA methylation following cell exposure to nano-HAp. Collectively, the results reveal the novel epigenetic regulation of cell function by nano-HAp which has significant implication on lineage determination as well as identifying a novel potential therapeutic use of nanomaterials. |
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| Keywords: | Hydroxyapatite Nanoparticle Gene expression Alkaline phosphatase Osteoblast Osteogenesis |
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