Journal of Cellular Biochemistry

Noggin suppression decreases BMP-2-induced osteogenesis of human bone marrow-derived mesenchymal stem cells In Vitro

Authors

  • Chao Chen,

    1. Department of Surgery, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, Canada
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  • Hasan Uludağ,

    1. Department of Biomedical Engineering, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Canada
    2. Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Canada
    3. Department of Chemical and Material Engineering, Faculty of Engineering, University of Alberta, Edmonton, Canada
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  • Zhixiang Wang,

    1. Department of Cell Biology, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Canada
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  • Hongxing Jiang MD

    Corresponding author
    1. Department of Surgery, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, Canada
    • Orthopaedic Consultants, 10972 - 124 Street Edmonton, Alberta, Canada T5M 0H8.
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  • The authors declare that they have no conflict of interest.

Abstract

Numerous studies with rodent cells and animal models indicate that noggin inhibits osteogenesis by antagonizing bone morphogenetic proteins (BMPs); however, the effect of noggin on osteogenesis of human cells remains ambiguous. This study aims to examine the effects of noggin suppression on viability and BMP-2-induced osteogenic differentiation of human bone marrow-derived mesenchymal stem cells (MSCs) in vitro. Noggin expression in human MSCs was suppressed by noggin-specific small interfering RNA (siRNA), and viability of human MSCs was determined by measuring the mitochondrial dehydrogenase activity, cellular DNA content and protein amount. The BMP-2-induced osteogenic differentiation of human MSCs was assessed by analyzing the expression levels of several osteoblastic genes, enzymatic alkaline phosphatase (ALP) activity and calcification. Our study showed that noggin suppression significantly decreased human MSC metabolism and DNA content on Days 3 and 6, and decreased total protein amount on Day 14. Noggin suppression also reduced the expression levels of osteoblastic genes, ALP, integrin-binding sialoprotein (IBSP), muscle segment homeobox gene (MSX2), osteocalcin (OC), osteopontin (OPN), and runt-related transcription factor-2 (RUNX2). Significantly decreased enzymatic ALP activity in noggin-suppressed group was evident. Moreover, noggin suppression decreased calcium deposits by BMP-2-induced osteoblasts. Collectively, this study showed that noggin suppression decreased viability and BMP-2-induced osteogenic differentiation of human MSCs, which suggests that noggin is stimulatory to osteogenesis of human MSCs. J. Cell. Biochem. 113: 3672–3680, 2012. © 2012 Wiley Periodicals, Inc.

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