Inhibition of overactive TGF-β attenuates progression of heterotopic ossification in mice

Xiao Wang, Fengfeng Li, Liang Xie, Janet Crane, Gehua Zhen, Yuji Mishina, Ruoxian Deng, Bo Gao, Hao Chen, Shen Liu, Ping Yang, Manman Gao, Manli Tu, Yiguo Wang, Mei Wan, Cunyi Fan and Xu Cao ()
Additional contact information
Xiao Wang: Johns Hopkins University
Fengfeng Li: Shanghai Sixth People’s Hospital
Liang Xie: Johns Hopkins University
Janet Crane: Johns Hopkins University
Gehua Zhen: Johns Hopkins University
Yuji Mishina: University of Michigan
Ruoxian Deng: Johns Hopkins University
Bo Gao: Johns Hopkins University
Hao Chen: Johns Hopkins University
Shen Liu: Johns Hopkins University
Ping Yang: Johns Hopkins University
Manman Gao: Johns Hopkins University
Manli Tu: Johns Hopkins University
Yiguo Wang: Johns Hopkins University
Mei Wan: Johns Hopkins University
Cunyi Fan: Shanghai Sixth People’s Hospital
Xu Cao: Johns Hopkins University

Nature Communications, 2018, vol. 9, issue 1, 1-13

Abstract: Abstract Acquired heterotopic ossification (HO) is a painful and debilitating disease characterized by extraskeletal bone formation after injury. The exact pathogenesis of HO remains unknown. Here we show that TGF-β initiates and promotes HO in mice. We find that calcified cartilage and newly formed bone resorb osteoclasts after onset of HO, which leads to high levels of active TGF-β that recruit mesenchymal stromal/progenitor cells (MSPCs) in the HO microenvironment. Transgenic expression of active TGF-β in tendon induces spontaneous HO, whereas systemic injection of a TGF-β neutralizing antibody attenuates ectopic bone formation in traumatic and BMP-induced mouse HO models, and in a fibrodysplasia ossificans progressive mouse model. Moreover, inducible knockout of the TGF-β type II receptor in MSPCs inhibits HO progression in HO mouse models. Our study points toward elevated levels of active TGF-β as inducers and promoters of ectopic bone formation, and suggest that TGF-β might be a therapeutic target in HO.

Date: 2018
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-018-02988-5 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-02988-5

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-018-02988-5

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().