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Review
. 2013 Oct 1;2(4):e24931.
doi: 10.4161/jkst.24931. Epub 2013 May 7.

JAK2-STAT5B pathway and osteoblast differentiation

Pramod Darvin  1 , Youn Hee Joung  1 , Young Mok Yang  1
Affiliations
Review

JAK2-STAT5B pathway and osteoblast differentiation

Pramod Darvin et al. JAKSTAT. .

Abstract

Osteoblast differentiation is a critical step in the maintenance of bone homeostasis. Osteoblast differentiation is generally maintained by growth hormone (GH) and various other endocrine and autocrine/paracrine factors. JAK2-STAT5B pathway is a central axis in the mechanism of GH signaling. Similarly, the autocrine/paracrine signaling factor IGF-1 also mediates its effects through this pathway. Analysis on JAK2-STAT5B pathway showed its importance in the IGF-1/IGF-1R mediated regulation of gene expression and osteoblast differentiation. Persistent activation of STAT5B and inhibition of STAT5B degradation showed increased osteoblastic differentiation and STAT5B/Runx-2 activities. Conditional gene silencing studies showed the importance of the JAK2-STAT5B pathway in stimulation of other transcription factors and expression of various differentiation markers.

Keywords: BMPs; IGF-1R; JAK2-STAT5B; growth hormone receptor; osteoblast differentiation.

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Figures

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Figure 1. Different cells of bone maintenance and homeostasis. Osteoblasts are differentiated from mesenchymal cell precursors. The mature osteoblast then differentiated into osteocytes and lining cells. These constitutes most of bones cells and protect bone from mechanical damages.
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Figure 2. GH transmits the signal in two phases. In the first phase (represented as dark arrow), GH binds to the GHR and triggers the JAK2-STAT5B signaling axis. This leads to the transcription of IGF-1 and IGF-1R. These then mediates the second phase (represented by dotted arrows) of signal transduction. Here IGF-1 binds to IGF-1R and triggers the MAPK pathway or PI3K/Akt pathway and induces osteoblast proliferation and differentiation.
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Figure 3. Regulation of Runx-2 activity by combined effect of STAT5B and Smad complexes. Induction of STAT5B from GH signaling leads to the formation of STAT5B/Runx-2 complex. Similarly, the Smad complexes induced by the action of BMP will bind with the Runx-2 and form Smad/STAT5B/Runx-2 complex and induce the transcription of genes responsible for osteoblast differentiation.
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