Mechanical stress determines the configuration of TGFβ activation in articular cartilage

Gehua Zhen, Qiaoyue Guo, Yusheng Li, Chuanlong Wu, Shouan Zhu, Ruomei Wang, X. Edward Guo, Byoung Choul Kim, Jessie Huang, Yizhong Hu, Yang Dan, Mei Wan, Taekjip Ha, Steven An and Xu Cao ()
Additional contact information
Gehua Zhen: The Johns Hopkins University
Qiaoyue Guo: The Johns Hopkins University
Yusheng Li: The Johns Hopkins University
Chuanlong Wu: The Johns Hopkins University
Shouan Zhu: The Johns Hopkins University
Ruomei Wang: The Johns Hopkins University
X. Edward Guo: Columbia University
Byoung Choul Kim: The Johns Hopkins University
Jessie Huang: The State University of New Jersey
Yizhong Hu: Columbia University
Yang Dan: The Johns Hopkins University
Mei Wan: The Johns Hopkins University
Taekjip Ha: The Johns Hopkins University
Steven An: The State University of New Jersey
Xu Cao: The Johns Hopkins University

Nature Communications, 2021, vol. 12, issue 1, 1-16

Abstract: Abstract Our incomplete understanding of osteoarthritis (OA) pathogenesis has significantly hindered the development of disease-modifying therapy. The functional relationship between subchondral bone (SB) and articular cartilage (AC) is unclear. Here, we found that the changes of SB architecture altered the distribution of mechanical stress on AC. Importantly, the latter is well aligned with the pattern of transforming growth factor beta (TGFβ) activity in AC, which is essential in the regulation of AC homeostasis. Specifically, TGFβ activity is concentrated in the areas of AC with high mechanical stress. A high level of TGFβ disrupts the cartilage homeostasis and impairs the metabolic activity of chondrocytes. Mechanical stress stimulates talin-centered cytoskeletal reorganization and the consequent increase of cell contractile forces and cell stiffness of chondrocytes, which triggers αV integrin–mediated TGFβ activation. Knockout of αV integrin in chondrocytes reversed the alteration of TGFβ activation and subsequent metabolic abnormalities in AC and attenuated cartilage degeneration in an OA mouse model. Thus, SB structure determines the patterns of mechanical stress and the configuration of TGFβ activation in AC, which subsequently regulates chondrocyte metabolism and AC homeostasis.

Date: 2021
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-021-21948-0 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:12:y:2021:i:1:d:10.1038_s41467-021-21948-0

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

DOI: 10.1038/s41467-021-21948-0

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 ().