The molecular mechanisms responsible for initiation and progression of osteoarthritis (OA) are incompletely understood. New data implicate cholesterol, its metabolites and the receptor RORα as catabolic drivers of OA-like disease in mice, but do these data identify new targets for treating patients with OA?
This is a preview of subscription content, access via your institution
Access options
Access Nature and 54 other Nature Portfolio journals
Get Nature+, our best-value online-access subscription
$29.99 / 30 days
cancel any time
Subscribe to this journal
Receive 12 print issues and online access
$209.00 per year
only $17.42 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
References
Zai, G. Alteration of metabolic pathways in osteoarthritis. Metabolites 9, 11 (2019).
Choi, W. S. et al. The CH25H–CYP7B1–RORα axis of cholesterol metabolism regulates osteoarthritis. Nature 566, 254–258 (2019).
Sun, M. M., Beier, F. & Ratneswaran, A. Nuclear receptors as emerging drug targets in osteoarthritis. Curr. Opin. Pharmacol. 40, 81–86 (2018).
Ali, S. A. et al. Regulation of cholesterol homeostasis by Hedgehog signaling in osteoarthritic cartilage. Arthritis Rheumatol. 68, 127–137 (2016).
Farnaghi, S. et al. Cholesterol metabolism in pathogenesis of osteoarthritis disease. Int. J. Rheum. Dis. 20, 127–130 (2017).
Woods, A. et al. Control of chondrocyte gene expression by actin dynamics: a novel role of cholesterol/ROR-alpha signalling in endochondral bone growth. J. Cell. Mol. Med. 13, 3497–3516 (2009).
Yamashita, A. et al. Statin treatment rescues FGFR3 skeletal dysplasia phenotypes. Nature 513, 507–511 (2014).
Tang, J. et al. Fibroblast growth factor receptor 3 inhibits osteoarthritis progression in the knee joints of adult mice. Arthritis Rheumatol. 68, 2432–2443 (2016).
Ikonen, E. Cellular cholesterol trafficking and compartmentalization. Nat. Rev. Mol. Cell Biol. 9, 125–138 (2008).
Sidman, R. L., Lane, P. W. & Dickie, M. M. Staggerer, a new mutation in the mouse affecting the cerebellum. Science 137, 610–612 (1962).
Acknowledgements
The author thanks the Canadian Institutes of Health Research (CIHR), the Arthritis Society and the Canada Research Chair Program for funding his research, and all the members of his lab for ongoing discussions.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Competing interests
The author declares no competing interests.
Rights and permissions
About this article
Cite this article
Beier, F. Cholesterol and cartilage do not mix well. Nat Rev Rheumatol 15, 253–254 (2019). https://doi.org/10.1038/s41584-019-0204-z
Published:
Issue Date:
DOI: https://doi.org/10.1038/s41584-019-0204-z
