Skip to Content
MilliporeSigma
  • Mechanosensor polycystin-1 potentiates differentiation of human osteoblastic cells by upregulating Runx2 expression via induction of JAK2/STAT3 signaling axis.

Mechanosensor polycystin-1 potentiates differentiation of human osteoblastic cells by upregulating Runx2 expression via induction of JAK2/STAT3 signaling axis.

Cellular and molecular life sciences : CMLS (2016-10-05)
Georgia Dalagiorgou, Christina Piperi, Christos Adamopoulos, Urania Georgopoulou, Antonios N Gargalionis, Anastasia Spyropoulou, Ilianna Zoi, Marjan Nokhbehsaim, Anna Damanaki, James Deschner, Efthimia K Basdra, Athanasios G Papavassiliou
ABSTRACT

Polycystin-1 (PC1) has been proposed as a chief mechanosensing molecule implicated in skeletogenesis and bone remodeling. Mechanotransduction via PC1 involves proteolytic cleavage of its cytoplasmic tail (CT) and interaction with intracellular pathways and transcription factors to regulate cell function. Here we demonstrate the interaction of PC1-CT with JAK2/STAT3 signaling axis in mechanically stimulated human osteoblastic cells, leading to transcriptional induction of Runx2 gene, a master regulator of osteoblastic differentiation. Primary osteoblast-like PC1-expressing cells subjected to mechanical-stretching exhibited a PC1-dependent increase of the phosphorylated(p)/active form of JAK2. Specific interaction of PC1-CT with pJAK2 was observed after stretching while pre-treatment of cells with PC1 (anti-IgPKD1) and JAK2 inhibitors abolished JAK2 activation. Consistently, mechanostimulation triggered PC1-mediated phosphorylation and nuclear translocation of STAT3. The nuclear phosphorylated(p)/DNA-binding competent pSTAT3 levels were augmented after stretching followed by elevated DNA-binding activity. Pre-treatment with a STAT3 inhibitor either alone or in combination with anti-IgPKD1 abrogated this effect. Moreover, PC1-mediated mechanostimulation induced elevation of Runx2 mRNA levels. ChIP assays revealed direct regulation of Runx2 promoter activity by STAT3/Runx2 after mechanical-stretching that was PC1-dependent. Our findings show that mechanical load upregulates expression of Runx2 gene via potentiation of PC1-JAK2/STAT3 signaling axis, culminating to possibly control osteoblastic differentiation and ultimately bone formation.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Duolink® In Situ PLA® Probe Anti-Goat PLUS
SKU
Pack Size
Availability
Price
Quantity
Sigma-Aldrich
Duolink® In Situ Detection Reagents Green
SKU
Pack Size
Availability
Price
Quantity
Sigma-Aldrich
Duolink® In Situ PLA® Probe Anti-Rabbit MINUS
SKU
Pack Size
Availability
Price
Quantity
Sigma-Aldrich
Duolink® In Situ Wash Buffer, Brightfield
SKU
Pack Size
Availability
Price
Quantity
Sigma-Aldrich
Duolink® In Situ Wash Buffers, Fluorescence
SKU
Pack Size
Availability
Price
Quantity
Sigma-Aldrich
Duolink® In Situ Probemaker MINUS
SKU
Pack Size
Availability
Price
Quantity
Sigma-Aldrich
Duolink® In Situ PLA® Probe Anti-Mouse PLUS
SKU
Pack Size
Availability
Price
Quantity
Sigma-Aldrich
Duolink® In Situ Detection Reagents Brightfield
SKU
Pack Size
Availability
Price
Quantity
Sigma-Aldrich
Duolink® In Situ Detection Reagents Orange
SKU
Pack Size
Availability
Price
Quantity
Sigma-Aldrich
Duolink® In Situ Detection Reagents FarRed
SKU
Pack Size
Availability
Price
Quantity
Sigma-Aldrich
Duolink® In Situ Orange Starter Kit Mouse/Rabbit
SKU
Pack Size
Availability
Price
Quantity
Sigma-Aldrich
Duolink® flowPLA Detection Kit - Orange, Duolink® PLA kit for Flow Cytometry with Orange Detection
SKU
Pack Size
Availability
Price
Quantity
Sigma-Aldrich
Duolink® flowPLA Detection Kit - FarRed, Duolink® PLA kit for Flow Cytometry with FarRed Detection
SKU
Pack Size
Availability
Price
Quantity
Sigma-Aldrich
Duolink® PLA Control Kit - PPI, Control Kit to reliably detect Protein-Protein Interactions (PPI) with Duolink® PLA
SKU
Pack Size
Availability
Price
Quantity
Sigma-Aldrich
Duolink® In Situ Microplate Nuclear Stain, Anti-Fade
SKU
Pack Size
Availability
Price
Quantity
Sigma-Aldrich
Duolink® In Situ PLA® Probe Anti-Rabbit PLUS, Affinity purified Donkey anti-Rabbit IgG (H+L)
SKU
Pack Size
Availability
Price
Quantity
Sigma-Aldrich
Duolink® In Situ Red Starter Kit Mouse/Rabbit
SKU
Pack Size
Availability
Price
Quantity
Sigma-Aldrich
Duolink® flowPLA Detection Kit - Red, DUOLINK® : PLA kit for Flow Cytometry with Red Detection
SKU
Pack Size
Availability
Price
Quantity
Sigma-Aldrich
Duolink® flowPLA Detection Kit - Green, Duolink® PLA kit for Flow Cytometry with Green Detection
SKU
Pack Size
Availability
Price
Quantity
Sigma-Aldrich
Duolink® In Situ Red Starter Kit Mouse/Goat
SKU
Pack Size
Availability
Price
Quantity
Sigma-Aldrich
Duolink® In Situ Orange Starter Kit Mouse/Goat
SKU
Pack Size
Availability
Price
Quantity
Sigma-Aldrich
Duolink® In Situ Red Starter Kit Goat/Rabbit
SKU
Pack Size
Availability
Price
Quantity
Sigma-Aldrich
Duolink® In Situ Orange Starter Kit Goat/Rabbit
SKU
Pack Size
Availability
Price
Quantity
Sigma-Aldrich
Duolink® In Situ Microplate Heat Transfer Block
SKU
Pack Size
Availability
Price
Quantity
Sigma-Aldrich
Duolink® In Situ PLA® Probe Anti-Mouse MINUS, Affinity purified Donkey anti-Mouse IgG (H+L)
SKU
Pack Size
Availability
Price
Quantity
Sigma-Aldrich
Duolink® In Situ Mounting Medium with DAPI
SKU
Pack Size
Availability
Price
Quantity
Sigma-Aldrich
Duolink® In Situ PLA® Probe Anti-Goat MINUS, Affinity purified Donkey anti-Goat IgG (H+L)
SKU
Pack Size
Availability
Price
Quantity
Sigma-Aldrich
Duolink® In Situ Detection Reagents Red
SKU
Pack Size
Availability
Price
Quantity
Sigma-Aldrich
Duolink® In Situ Probemaker PLUS
SKU
Pack Size
Availability
Price
Quantity