Abstract
Osteoarthritis, a highly prevalent degenerative joint disorder, is characterized by joint pain and disability. Available treatments fail to modify osteoarthritis progression and decrease joint pain effectively. Here, we show that intermittent parathyroid hormone (iPTH) attenuates osteoarthritis pain by inhibiting subchondral sensory innervation, subchondral bone deterioration, and articular cartilage degeneration in a destabilized medial meniscus (DMM) mouse model. We found that subchondral sensory innervation for osteoarthritis pain was significantly decreased in PTH-treated DMM mice compared with vehicle-treated DMM mice. In parallel, deterioration of subchondral bone microarchitecture in DMM mice was attenuated by iPTH treatment. Increased level of prostaglandin E2 in subchondral bone of DMM mice was reduced by iPTH treatment. Furthermore, uncoupled subchondral bone remodeling caused by increased transforming growth factor β signaling was regulated by PTH-induced endocytosis of the PTH type 1 receptor–transforming growth factor β type 2 receptor complex. Notably, iPTH improved subchondral bone microarchitecture, and decreased level of prostaglandin E2 and sensory innervation of subchondral bone in DMM mice by acting specifically through PTH type 1 receptor in Nestin+ mesenchymal stromal cells. Thus, iPTH could be a potential disease-modifying therapy for osteoarthritis.
Data availability
All data generated or analysed during this study are included in the manuscript and supporting files
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Author details
Funding
National Institutes of Health (P01AG066603)
- Xu Cao
National Institutes of Health (1R01 AG068997)
- Xu Cao
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: Ethics Statement: All animal experiments were approved by the Institutional Animal Care and Use of Johns Hopkins University, School of Medicine. (Protocol number: Mo18M308).
Copyright
© 2021, Sun et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Parathyroid hormone attenuates osteoarthritis pain by remodeling subchondral bone in mice
eLife 10:e66532.
https://doi.org/10.7554/eLife.66532
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