Intermittent Administration of Parathyroid Hormone 1-34 Enhances Osteogenesis of Human Mesenchymal Stem Cells by Regulating Protein Kinase Cδ

• Published in: International journal of molecular sciences Vol. 18; no. 10; p. 2221
• Main Authors: Kuo, Shu-Wen, Rimando, Marilyn G, Liu, Yi-Shiuan, Lee, Oscar K
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 24-10-2017; MDPI
• Subjects: Alkaline phosphatase; Biocompatibility; Cbfa-1 protein; Chemical stimuli; Collagen (type I); Cues; Differentiation; Gene expression; Genes; human mesenchymal stem cells; Kinases; Mesenchyme; Osteoblastogenesis; Osteoblasts; Osteogenesis; Parathyroid; Parathyroid hormone; PKCδ; Protein kinase C; Signal transduction; Stem cells; Transcription activation; parathyroid hormone; PKCδ; osteogenesis; human mesenchymal stem cells
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms18102221

Human mesenchymal stem cells (hMSCs) can differentiate into osteoblasts and are regulated by chemical cues. The recombinant N-terminal (1-34 amino acids) fragment of the parathyroid hormone (PTH (1-34)) is identified to promote osteogenesis. The osteoanabolic effects of intermittent PTH (1-34) treatment are linked to a complex consisting of signaling pathways; additionally, protein kinase C (PKC) act as mediators of multifunctional signaling transduction pathways, but the role of PKC δ (PKCδ), a downstream target in regulating osteoblast differentiation during intermittent administration of PTH (1-34) is less studied and still remains elusive. The purpose of this study is to examine the role of PKCδ during intermittent and continuous PTH (1-34) administration using osteoblast-lineage-committed hMSCs. Relative gene expression of osteoblast-specific genes demonstrated significant upregulation of
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and increased alkaline phosphatase activity in the presence of PTH (1-34). Intermittent PTH (1-34) administration increased PKC activity at day 7 of osteogenic differentiation, whereas inhibition of PKC activity attenuated these effects. In addition, the specific isoform PKCδ was activated upon treatment. These findings demonstrate that intermittent PTH (1-34) treatment enhances the osteogenesis of hMSCs by upregulating osteoblast-specific genes via PKCδ activation.