Targeting mechanosignalling in cartilage repair an emerging paradigm in the treatment of osteoarthritis Tom.pdf (1.04 MB)
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Mechanosignalling in cartilage: an emerging target for the treatment of osteoarthritis

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posted on 2023-03-01, 17:46 authored by Tom HodgkinsonTom Hodgkinson, Domhnall Kelly, Caroline CurtinCaroline Curtin, Fergal O'BrienFergal O'Brien
Mechanical stimuli have fundamental roles in articular cartilage during health and disease. Chondrocytes respond to the physical properties of the cartilage extracellular matrix (ECM) and the mechanical forces exerted on them during joint loading. In osteoarthritis (OA), catabolic processes degrade the functional ECM and the composition and viscoelastic properties of the ECM produced by chondrocytes are altered. The abnormal loading environment created by these alterations propagates cell dysfunction and inflammation. Chondrocytes sense their physical environment via an array of mechanosensitive receptors and channels that activate a complex network of downstream signalling pathways to regulate several cell processes central to OA pathology. Advances in understanding the complex roles of specific mechanosignalling mechanisms in healthy and OA cartilage have highlighted molecular processes that can be therapeutically targeted to interrupt pathological feedback loops. The potential for combining these mechanosignalling targets with the rapidly expanding field of smart mechanoresponsive biomaterials and delivery systems is an emerging paradigm in OA treatment. The continued advances in this field have the potential to enable restoration of healthy mechanical microenvironments and signalling through the development of precision therapeutics, mechanoregulated biomaterials and drug systems in the near future.

Funding

Marie Skłodowska-Curie Individual Fellowship from the European Commission through the H2020, project ChondroCONNECT (Project ID: 894837)

Science Foundation Ireland (SFI) under the European Regional Development Fund CÚRAM (13/RC/2073)

Irish Research Council Government of Ireland Postgraduate Program (GOIPG/2018/371)

Irish Health Research Board (HRB) ILP-POR-2019-023 and ILP-POR-2017-032

European Community’s Horizon 2020 research and innovation programme under ERC Advanced Grant agreement number 788753 (ReCaP)

Irish Health Research Board (HRB) ILP-POR-2017-032

History

Comments

The original article is available at https://www.nature.com/

Published Citation

Hodgkinson T, Kelly DC, Curtin CM, O'Brien FJ. Mechanosignalling in cartilage: an emerging target for the treatment of osteoarthritis. Nat Rev Rheumatol. 2022;18(2):67-84.

Publication Date

21 December 2021

PubMed ID

34934171

Department/Unit

  • Tissue Engineering Research Group (TERG)
  • Anatomy and Regenerative Medicine
  • Amber (Advanced Material & Bioengineering Research) Centre

Research Area

  • Immunity, Infection and Inflammation
  • Chemistry and Pharmaceutical Sciences
  • Biomaterials and Regenerative Medicine

Publisher

Springer Nature Limited

Version

  • Accepted Version (Postprint)