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PPARγ/mTOR signalling: striking the right balance in cartilage homeostasis
  1. Francesco Dell'Accio1,
  2. Joanna Sherwood2
  1. 1William Harvey Research Institute, Barts and The London, School of Medicine and Dentistry, Queen Mary, University of London, London, UK
  2. 2Institute for Experimental Musculoskeletal Medicine, University Hospital Münster, Münster, Germany
  1. Correspondence to Professor Francesco Dell'Accio, William Harvey Research Institute, Barts and The London, School of Medicine and Dentistry, Queen Mary, University of London, J Vane Centre, Charterhouse Square, London, EC1M 6BQ, UK; f.dellaccio{at}

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Osteoarthritis (OA) is still a highly prevalent and disabling disease for which we do not have a cure. In the last decade, however, the unravelling of molecular mechanisms controlling joint homeostasis, the advances in targeting technologies, and the improvement of animal models allowing the use of mouse genetics has led to the identification of molecular targets that, in animal models,1–4 and possibly also in humans5 can arrest disease or even revert its course. Such strategies include blockade of extracellular matrix-degrading enzymes,6 hypoxia-inducible factor 2α blockade3 ,4 to prevent chondrocyte hypertrophy, the support of parathyroid hormone/parathyroid hormone related protein signalling—an injury-induced homeostatic mechanism affecting both cartilage homeostasis and bone remodelling,2 improving bone turnover using strontium ranelate,5 and blockade of the filamin-core binding factor interaction thereby supporting chondrocytic differentiation using kartogenin.7 Although only strontium ranelate has been tested in the clinic, there is little doubt that the availability of multiple targets will stimulate and instruct the experimentation needed to bridge the gap to the clinic.

In this issue of the journal, Vasheghani et al8 have demonstrated that PPARγ-driven mTOR (mammalian target of rapamycin) inhibition protects cartilage from experimental OA, at least in part by supporting autophagy,8 a process that, by suppressing protein synthesis and enabling the use of cellular components to generate energy, allows cells to escape death in conditions of stress or lack of nutrients.9

The authors previously reported that cartilage-specific disruption of the gene encoding for the transcription factor PPARγ results in spontaneous OA in mice.10 To ensure that this phenotype was not driven by skeletal dysplasia determined by the absence of PPARγ during development, they generated a new mutant in which PPARγ could be deleted postnatally in chondrocytes upon administration of doxycycline. The mice did not develop …

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  • Contributors FD and JS have both contributed to writing the manuscript.

  • Competing interests None.

  • Provenance and peer review Commissioned; externally peer reviewed.

  • Open Access This is an Open Access article distributed in accordance with the terms of the Creative Commons Attribution (CC BY 4.0) license, which permits others to distribute, remix, adapt and build upon this work, for commercial use, provided the original work is properly cited. See:

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