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Int. J. Mol. Sci. 2017, 18(1), 159; doi:10.3390/ijms18010159

Osteocalcin Mediates Biomineralization during Osteogenic Maturation in Human Mesenchymal Stromal Cells

1
Institute of Clinical Medicine, National Yang-Ming University, Taipei 11221, Taiwan
2
Division of Nephrology, Department of Medicine, Taoyuan General Hospital, Ministry of Health and Welfare, Taoyuan 33004, Taiwan
3
Institute of Biophotonics, National Yang-Ming University, Taipei 11221, Taiwan
4
Stem Cell Research Center, National Yang-Ming University, Taipei 11221, Taiwan
5
Taipei City Hospital, Taipei 10341, Taiwan
6
Department of Medical Research, Taipei Veterans General Hospital, Taipei 11217, Taiwan
7
Department of Orthopaedics and Traumatology, Taipei Veterans General Hospital, Taipei 11217, Taiwan
*
Authors to whom correspondence should be addressed.
Academic Editor: Charles J. Malemud
Received: 2 November 2016 / Revised: 4 January 2017 / Accepted: 6 January 2017 / Published: 17 January 2017
(This article belongs to the Section Biochemistry, Molecular and Cellular Biology)
View Full-Text   |   Download PDF [5846 KB, uploaded 17 January 2017]   |  

Abstract

There is a growing interest in cell therapies using mesenchymal stromal cells (MSCs) for repairing bone defects. MSCs have the ability to differentiate into osteoprogenitors and osteoblasts as well as to form calcified bone matrix. However, the molecular mechanisms governing mineralization during osteogenic differentiation remain unclear. Non-collagenous proteins in the extracellular matrix are believed to control different aspects of the mineralization. Since osteocalcin is the most abundant non-collagenous bone matrix protein, the purpose of this study is to investigate the roles of osteocalcin in mineral species production during osteogenesis of MSCs. Using Raman spectroscopy, we found that the maturation of mineral species was affected by osteocalcin expression level. After osteocalcin was knocked down, the mineral species maturation was delayed and total hydroxyapatite was lower than the control group. In addition, the expression of osteogenic marker genes, including RUNX2, alkaline phosphatase, type I collagen, and osteonectin, was downregulated during osteogenic differentiation compared to the control group; whereas gene expression of osterix was upregulated after the knockdown. Together, osteocalcin plays an essential role for the maturation of mineral species and modulates osteogenic differentiation of MSCs. The results offer new insights into the enhancement of new bone formation, such as for the treatments of osteoporosis and fracture healing. View Full-Text
Keywords: mesenchymal stromal cells (MSCs); osteocalcin; osteogenic differentiation; non-collagenous protein; mineralization; hydroxyapatite; Raman spectroscopy mesenchymal stromal cells (MSCs); osteocalcin; osteogenic differentiation; non-collagenous protein; mineralization; hydroxyapatite; Raman spectroscopy
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MDPI and ACS Style

Tsao, Y.-T.; Huang, Y.-J.; Wu, H.-H.; Liu, Y.-A.; Liu, Y.-S.; Lee, O.K. Osteocalcin Mediates Biomineralization during Osteogenic Maturation in Human Mesenchymal Stromal Cells. Int. J. Mol. Sci. 2017, 18, 159.

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