Research Paper Volume 12, Issue 24 pp 24778—24797
L-PGDS deficiency accelerated the development of naturally occurring age-related osteoarthritis
- 1 Osteoarthritis Research Unit, University of Montreal Hospital Research Center (CRCHUM), and Department of Medicine, University of Montreal, Montreal, QC H2X 0A9, Canada
- 2 Faculty of Veterinary Medicine, Clinical Science, University of Montreal, Saint-Hyacinthe, QC, J2S 2M2, Canada
- 3 Isotope Science Center, The University of Tokyo, Yayoi, Bunkyo-ku, Tokyo 113-0032, Japan
- 4 Research Centre, Sacré-Coeur Hospital, University of Montreal, Montreal, QC H4J 1C5, Canada
Received: August 5, 2020 Accepted: November 3, 2020 Published: December 23, 2020https://doi.org/10.18632/aging.202367
How to Cite
Copyright: © 2020 Ouhaddi et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Osteoarthritis (OA) is the most common musculoskeletal disorder among the elderly. It is characterized by progressive cartilage degradation, synovial inflammation, subchondral bone remodeling and pain. Lipocalin prostaglandin D synthase (L-PGDS) is responsible for the biosynthesis of PGD2, which has been implicated in the regulation of inflammation and cartilage biology. This study aimed to evaluate the effect of L-PGDS deficiency on the development of naturally occurring age-related OA in mice.
OA-like structural changes were assessed by histology, immunohistochemistry, and micro–computed tomography. Pain related behaviours were assessed using the von Frey and the open-field assays.
L-PGDS deletion promoted cartilage degradation during aging, which was associated with enhanced expression of extracellular matrix degrading enzymes, matrix metalloprotease 13 (MMP-13) and a disintegrin and metalloproteinase with thrombospondin motifs 5 (ADAMTS-5), and their breakdown products, C1,2C, VDIPEN and NITEG. Moreover, L-PGDS deletion enhanced subchondral bone changes, but had no effect on its angiogenesis. Additionally, L-PGDS deletion increased mechanical sensitivity and reduced spontaneous locomotor activity. Finally, we showed that the expression of L-PGDS was elevated in aged mice. Together, these findings indicate an important role for L-PGDS in naturally occurring age-related OA. They also suggest that L-PGDS may constitute a new efficient therapeutic target in OA.