# The role of YAP and TAZ transcriptional coactivators in osteoblast lineage cells

> **NIH NIH P20** · UNIV OF ARKANSAS FOR MED SCIS · 2020 · $301,686

## Abstract

PROJECT SUMMARY/ABSTRACT
 Unbalanced bone remodeling often causes bone loss and leads to osteoporosis. Wnt/β-catenin signaling is
essential for commitment and differentiation of bone forming osteoblasts from mesenchymal progenitors.
Changes in mechanical loading can also influence bone formation. Osteocytes, former osteoblasts buried in
bone matrix, are thought to be the cells that perceive mechanical signals and orchestrate bone remodeling.
However, the molecular mechanisms by which osteocytes perceive and transduce mechanical signals are not
fully understood. YAP (Yes-associated protein) and TAZ (transcriptional co-activator with PDZ-binding motif),
two related transcriptional co-factors that shuttle between the cytoplasm and the nucleus, have emerged as
potentially important transcriptional regulators in mechanotransduction. Their activity is dependent on their
subcellular localization, which is tightly regulated by different extracellular cues. Cytoplasmic YAP and TAZ
promote proteosomal degradation of β-catenin and thereby inhibit Wnt signaling. Mechanical signals emanating
from rigid extracellular matrix or from fluid flow promote YAP and TAZ translocation into nucleus where they
stimulate transcription. Our preliminary studies show that deletion of YAP and TAZ from osteoblast progenitors
increased osteoblast formation in mice, and this was associated with increased Wnt signaling. In contrast,
deletion of YAP and TAZ from differentiated osteoblasts and osteocytes decreased osteoblast number and bone
formation. These results suggest that YAP and TAZ perform different functions in mesenchymal progenitors
versus mature osteoblasts and osteocytes. Based on this, we hypothesize that the less rigid environment of
osteoblast progenitors retains YAP and TAZ in the cytoplasm, promotes β-catenin degradation, and thereby
inhibits osteoblast differentiation. In contrast, the more rigid environment of osteoblasts and osteocytes, together
with other mechanical inputs (such as fluid shear), favors nuclear retention of YAP and TAZ and thereby
increases osteoblast number. To test this hypothesis, we will determine whether YAP and TAZ in osteoblast
progenitors inhibit their differentiation by promoting β-catenin degradation using genetically modified mice in
which YAP will be restricted to the cytoplasm or the nucleus (Aim 1). In addition, we will examine whether YAP
and TAZ expression in osteocytes mediates the effects of changes in mechanical loading on osteoblast number
using tail suspension and cyclic compression models (Aim 2). Further, we will perform in vitro studies to identify
YAP and TAZ target genes in osteoblasts and osteocytes that are responsible for their effects on osteoblast
number using genome-wide mRNA expression analysis (RNA-seq) in osteoblastic and osteocytic cells before
and after suppression of the endogenous YAP and TAZ genes (Aim 3). Successful completion of these studies
will shed light on novel mechanisms that control bone formati...

## Key facts

- **NIH application ID:** 9872191
- **Project number:** 5P20GM125503-03
- **Recipient organization:** UNIV OF ARKANSAS FOR MED SCIS
- **Principal Investigator:** Jinhu Xiong
- **Activity code:** P20 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $301,686
- **Award type:** 5
- **Project period:** — → —

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9872191

## Citation

> US National Institutes of Health, RePORTER application 9872191, The role of YAP and TAZ transcriptional coactivators in osteoblast lineage cells (5P20GM125503-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9872191. Licensed CC0.

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