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The changing role of TGFβ in healthy, ageing and osteoarthritic joints

  • Review Article
  • Published:

From Nature Reviews Rheumatology

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Key Points

  • Physiological loading of articular cartilage maintains transforming growth factor-β (TGFβ) signalling and prevents hypertrophic differentiation of articular chondrocytes

  • TGFβ signalling changes with ageing, at least in animal models, resulting in a loss of SMAD2–SMAD3 signalling and making articular cartilage prone to changes associated with osteoarthritis (OA)

  • Loading-induced induction of TGFβ signalling is less efficient in aged cartilage than in young cartilage, impairing the mechanism that blocks chondrocyte hypertrophic differentiation

  • During OA, high levels of active TGFβ in the joint drive fibrosis, osteophyte formation and subchondral bone changes

  • The role of TGFβ changes from protective in a young, healthy joint to pathologic in an osteoarthritic joint

Abstract

Transforming growth factor-β (TGFβ) is a pleiotropic cytokine that is important in the regulation of joint homeostasis and disease. TGFβ signalling is induced by loading and has an important function in maintaining the differentiated phenotype of articular chondrocytes. Concentrations of active TGFβ differ greatly between healthy and osteoarthritic joints, being low in healthy joints and high in osteoarthritic joints, leading to the activation of different signalling pathways in joint cells. The characteristic pathology of osteoarthritic joints, such as cartilage damage, osteophyte formation and synovial fibrosis, seems to be stimulated or even caused by the high levels of active TGFβ, in combination with altered chondrocyte signalling pathways (which are also observed in ageing joints). In this Review, the changing role of TGFβ in normal joint homeostasis, ageing and osteoarthritis is discussed: TGFβ counteracts pathological changes in a young healthy joint, alters its signalling during ageing and is a driving force of pathology in osteoarthritic joints.

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Figure 1: Simplified scheme of TGFβ signalling.
Figure 2: Model of loading-induced TGFβ signalling in articular cartilage.
Figure 3: Age-related changes in TGFβ signalling in articular cartilage.
Figure 4: Role of TGFβ in a normal and an osteoarthritic joint.

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  1. Department of Rheumatology, Radboudumc, Experimental Rheumatology, Geert Grooteplein 26–28, Nijmegen, 6525 GA, The Netherlands

    Peter M. van der Kraan

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van der Kraan, P. The changing role of TGFβ in healthy, ageing and osteoarthritic joints. Nat Rev Rheumatol 13, 155–163 (2017). https://doi.org/10.1038/nrrheum.2016.219

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