YAP regulates transcriptional programs for layer-specific periosteal expansion during fracture repair

Madhura P Nijsure; Brendan Tobin; Dakota L Jones; Annemarie Lang; Grey Hallström; Miriam Baitner; Gabrielle I Tanner; Georgios Kotsaris; Yasaman Moharrer; Christopher J Panebianco; Elizabeth G Seidl; Nathaniel A Dyment; Gregory L Szeto; Levi Wood; Joel D Boerckel

doi:10.1126/sciadv.adw0126

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$YAP regulates transcriptional programs for layer-specific periosteal expansion during fracture repair$

Journal article

Peer reviewed

YAP regulates transcriptional programs for layer-specific periosteal expansion during fracture repair

Madhura P Nijsure, Brendan Tobin, Dakota L Jones, Annemarie Lang, Grey Hallström, Miriam Baitner, Gabrielle I Tanner, Georgios Kotsaris, Yasaman Moharrer, Christopher J Panebianco, …

Science advances, Vol.11(32), p.eadw0126

08/08/2025

DOI: 10.1126/sciadv.adw0126

PMCID: PMC12327455

PMID: 40768586

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Abstract

Bone fracture repair initiates by periosteal expansion. The periosteum is a bilayered tissue composed of inner cambium and outer fibrous layers. Typically quiescent, periosteal progenitor cells proliferate upon fracture; however, the underlying transcriptional mechanisms remain unclear. Here, we show that deletion of the transcriptional regulators, yes-associated protein (YAP) and transcriptional coactivator with PDZ binding motif (TAZ), from Osterix-expressing cells, which reside in the cambium, impairs periosteal expansion. YAP activation increases chromatin accessibility, preferentially at TEA domain transcription factor (TEAD) binding sites, and regulates both cell-intrinsic and cell-extrinsic cellular functions. We identify bone morphogenetic protein 4 ( ) as a YAP-TEAD target gene expressed in the cambium. In YAP/TAZ knockout mice, BMP4 delivery increased periosteal expansion through matrix accumulation and fibrous layer cell proliferation. Conversely, in wild-type mice, BMP4 delivery increased osteogenic activity and angiogenesis. Together, these data identify YAP-mediated transcriptional programs that promote layer-specific periosteal expansion.

Adaptor Proteins, Signal Transducing - genetics

Adaptor Proteins, Signal Transducing - metabolism

Animals

Bone Morphogenetic Protein 4 - genetics

Bone Morphogenetic Protein 4 - metabolism

Cell Cycle Proteins - genetics

Cell Cycle Proteins - metabolism

Cell Proliferation

Fracture Healing - genetics

Gene Expression Regulation

Mice

Mice, Knockout

Osteogenesis - genetics

Periosteum - metabolism

Sp7 Transcription Factor - genetics

Sp7 Transcription Factor - metabolism

Transcription Factors - genetics

Transcription Factors - metabolism

Transcription, Genetic

YAP-Signaling Proteins

Details

Title: Subtitle: YAP regulates transcriptional programs for layer-specific periosteal expansion during fracture repair
Creators: Madhura P Nijsure - University of Pennsylvania
Brendan Tobin - Georgia Institute of Technology
Dakota L Jones - University of Iowa
Annemarie Lang - University of Pennsylvania
Grey Hallström - University of Pennsylvania
Miriam Baitner - University of Pennsylvania
Gabrielle I Tanner - University of Pennsylvania
Georgios Kotsaris - University of Pennsylvania
Yasaman Moharrer - University of Pennsylvania
Christopher J Panebianco - University of Pennsylvania
Elizabeth G Seidl - University of Pennsylvania
Nathaniel A Dyment - University of Pennsylvania
Gregory L Szeto - Pfizer (United States)
Levi Wood - Georgia Institute of Technology
Joel D Boerckel - University of Pennsylvania
Resource Type: Journal article
Publication Details: Science advances, Vol.11(32), p.eadw0126
DOI: 10.1126/sciadv.adw0126
PMID: 40768586
PMCID: PMC12327455
NLM abbreviation: Sci Adv
ISSN: 2375-2548
eISSN: 2375-2548
Publisher: AMER ASSOC ADVANCEMENT SCIENCE; WASHINGTON
Grant note: R01 AR074948 / NIAMS NIH HHS P30 AR050950 / NIAMS NIH HHS T32 AR007132 / NIAMS NIH HHS R01 AR073809 / NIAMS NIH HHS K12 GM081259 / NIGMS NIH HHS
Language: English
Date published: 08/08/2025
Academic Unit: Anatomy and Cell Biology
Record Identifier: 9984949264302771

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