ESPEYB16 5. Bone, Growth Plate and Mineral Metabolism Basic Science - Growth Plate (3 abstracts)
5.15. mir-374-5p, mir-379-5p, and mir-503-5p Regulate Proliferation and Hypertrophic Differentiation of Growth Plate Chondrocytes in Male Rats
Jee YH , Wang J , Yue S , Jennings M , Clokie SJ , Nilsson O , Lui JC & Baron J
Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland
Abstract: Endocrinology. 2018 Mar 1;159(3):1469–1478.
In brief: In this article, a combination of microdissection, miroRNA profiling and transfection studies identify 3 microRNAs that are highly expressed in the proliferative zone and appear to be down-stream mediators of PTHrP signaling in the growth plate.
Comment: In the growth plate, PTHrP act as a paracrine factor that maintains chondrocytes in the proliferative pool by inhibiting hypertrophic differentiation and is thus crucial for normal growth plate chondrogenesis and longitudinal bone growth. However, the understanding of the downstream mediators of PTHrP signaling is limited. Recently, cartilage-specific ablation of Dicer result in dwarfism due to decreased proliferation and accelerated differentiation of growth plate chondrocytes.
These authors used a combination of miRNA profiling and transfection studies to identify specific miRNAs that are highly expressed in the proliferative zone and promote proliferation and inhibit expression of hypertrophic chondrocyte marker genes. Three out of four miRNAs were also found to be directly regulated by PTH 1-34, indicating that the identified miRNAs are downstream mediators of PTHrP signaling in proliferative chondrocytes and hence act to maintain chondrocytes in the proliferative pool. This work indicates that PTHrP signaling in the growth plate is, at least in part, mediated through regulation of miRNA.
This study identifies a novel mechanism by which paracrine signals in the growth plate (and other tissues) may be mediated and also point to novel signaling pathways that may be targeted for treatments of growth disorders.
Volume 16
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ESPE Yearbook of Paediatric Endocrinology
ISSN 1662-4009 (Online)
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