Identification of novel genes in aging osteoblasts using next-generation sequencing and bioinformatics
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Yi-Jen Chen1,2, Wei-An Chang1,3, Ming-Shyan Huang4,5, Chia-Hsin Chen2,6, Kuan-Yuan Wang7, Ya-Ling Hsu8 and Po-Lin Kuo1,8,9
1Graduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
2Department of Physical Medicine and Rehabilitation, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
3Division of Pulmonary and Critical Care Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
4Department of Internal Medicine, E-DA Cancer Hospital, Kaohsiung, Taiwan
5School of Medicine, I-Shou University, Kaohsiung, Taiwan
6Department of Physical Medicine and Rehabilitation, School of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
7Division of Geriatrics and Gerontology, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
8Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
9Institute of Medical Science and Technology, National Sun Yat-Sen University, Kaohsiung, Taiwan
Ya-Ling Hsu, email: [email protected]
Po-Lin Kuo, email: [email protected]
Keywords: aging osteoblasts; next-generation sequencing; bioinformatics; microRNA; messenger RNA
Received: September 08, 2017 Accepted: October 27, 2017 Published: November 28, 2017
During the aging process, impaired osteoblastic function is one key factor of imbalanced bone formation and age-related bone loss. The aim of this study is to explore the differentially expressed genes in normal and aged osteoblasts and to identify genes potentially involved in age-related alteration in bone physiology. Based on next generation sequencing and bioinformatics analysis, 12 differentially expressed microRNAs and 22 differentially expressed genes were identified. Up-regulation of miR-204-5p was validated in an array of osteoporotic hip fracture in the Gene Expression Omnibus database (GSE74209). The putative targets for miR-204-5p were Kruppel-like factor 7 (KLF7) and SRY-box 11 (SOX11). Ingenuity Pathway Analysis identified SOX11, involved in osteoarthritis pathway and differentiation of osteoblasts, together with miR-204-5p, a potential upstream regulator, suggesting the critical role of miR-204-5p-SOX11 regulation in the aging process of human bones. In addition, as semaphorin 3A (SEMA3A) and ephrin type-A receptor 5 (EPHA5) were involved in nervous system related biological functions, we postulated a potential linkage between SEMA3A, EPHA5 and development of neurogenic heterotopic ossification. Our findings implicate new candidate genes in the diagnosis of geriatric musculoskeletal disorders, and provide novel insights that may contribute to the elaboration of new biomarkers for neurogenic heterotopic ossification.
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