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Inhibition of PGE2 in Subchondral Bone Attenuates Osteoarthritis

Aberrant subchondral bone architecture is a crucial driver of the pathological progression of osteoarthritis, coupled with increased sensory innervation. The sensory PGE2/EP4 pathway is involved in the regulation of bone mass accrual by the induction of differentiation of mesenchymal stromal cells....

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Autores principales: Sun, Qi, Zhang, Yuanzhen, Ding, Yilan, Xie, Wenqing, Li, Hengzhen, Li, Shaohua, Li, Yusheng, Cai, Ming
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9454853/
https://www.ncbi.nlm.nih.gov/pubmed/36078169
http://dx.doi.org/10.3390/cells11172760
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author Sun, Qi
Zhang, Yuanzhen
Ding, Yilan
Xie, Wenqing
Li, Hengzhen
Li, Shaohua
Li, Yusheng
Cai, Ming
author_facet Sun, Qi
Zhang, Yuanzhen
Ding, Yilan
Xie, Wenqing
Li, Hengzhen
Li, Shaohua
Li, Yusheng
Cai, Ming
author_sort Sun, Qi
collection PubMed
description Aberrant subchondral bone architecture is a crucial driver of the pathological progression of osteoarthritis, coupled with increased sensory innervation. The sensory PGE2/EP4 pathway is involved in the regulation of bone mass accrual by the induction of differentiation of mesenchymal stromal cells. This study aimed to clarify whether the sensory PGE2/EP4 pathway induces aberrant structural alteration of subchondral bone in osteoarthritis. Destabilization of the medial meniscus (DMM) using a mouse model was combined with three approaches: the treatment of celecoxib, capsaicin, and sensory nerve-specific prostaglandin E2 receptor 4 (EP4)-knockout mice. Cartilage degeneration, subchondral bone architecture, PGE2 levels, distribution of sensory nerves, the number of osteoprogenitors, and pain-related behavior in DMM mice were assessed. Serum and tissue PGE2 levels and subchondral bone architecture in a human sample were measured. Increased PGE2 is closely related to subchondral bone’s abnormal microstructure in humans and mice. Elevated PGE2 concentration in subchondral bone that is mainly derived from osteoblasts occurs in early-stage osteoarthritis, preceding articular cartilage degeneration in mice. The decreased PGE2 levels by the celecoxib or sensory denervation by capsaicin attenuate the aberrant alteration of subchondral bone architecture, joint degeneration, and pain. Selective EP4 receptor knockout of the sensory nerve attenuates the aberrant formation of subchondral bone and facilitates the prevention of cartilage degeneration in DMM mice. Excessive PGE2 in subchondral bone caused a pathological alteration to subchondral bone in osteoarthritis and maintaining the physiological level of PGE2 could potentially be used as an osteoarthritis treatment.
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spelling pubmed-94548532022-09-09 Inhibition of PGE2 in Subchondral Bone Attenuates Osteoarthritis Sun, Qi Zhang, Yuanzhen Ding, Yilan Xie, Wenqing Li, Hengzhen Li, Shaohua Li, Yusheng Cai, Ming Cells Article Aberrant subchondral bone architecture is a crucial driver of the pathological progression of osteoarthritis, coupled with increased sensory innervation. The sensory PGE2/EP4 pathway is involved in the regulation of bone mass accrual by the induction of differentiation of mesenchymal stromal cells. This study aimed to clarify whether the sensory PGE2/EP4 pathway induces aberrant structural alteration of subchondral bone in osteoarthritis. Destabilization of the medial meniscus (DMM) using a mouse model was combined with three approaches: the treatment of celecoxib, capsaicin, and sensory nerve-specific prostaglandin E2 receptor 4 (EP4)-knockout mice. Cartilage degeneration, subchondral bone architecture, PGE2 levels, distribution of sensory nerves, the number of osteoprogenitors, and pain-related behavior in DMM mice were assessed. Serum and tissue PGE2 levels and subchondral bone architecture in a human sample were measured. Increased PGE2 is closely related to subchondral bone’s abnormal microstructure in humans and mice. Elevated PGE2 concentration in subchondral bone that is mainly derived from osteoblasts occurs in early-stage osteoarthritis, preceding articular cartilage degeneration in mice. The decreased PGE2 levels by the celecoxib or sensory denervation by capsaicin attenuate the aberrant alteration of subchondral bone architecture, joint degeneration, and pain. Selective EP4 receptor knockout of the sensory nerve attenuates the aberrant formation of subchondral bone and facilitates the prevention of cartilage degeneration in DMM mice. Excessive PGE2 in subchondral bone caused a pathological alteration to subchondral bone in osteoarthritis and maintaining the physiological level of PGE2 could potentially be used as an osteoarthritis treatment. MDPI 2022-09-05 /pmc/articles/PMC9454853/ /pubmed/36078169 http://dx.doi.org/10.3390/cells11172760 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Sun, Qi
Zhang, Yuanzhen
Ding, Yilan
Xie, Wenqing
Li, Hengzhen
Li, Shaohua
Li, Yusheng
Cai, Ming
Inhibition of PGE2 in Subchondral Bone Attenuates Osteoarthritis
title Inhibition of PGE2 in Subchondral Bone Attenuates Osteoarthritis
title_full Inhibition of PGE2 in Subchondral Bone Attenuates Osteoarthritis
title_fullStr Inhibition of PGE2 in Subchondral Bone Attenuates Osteoarthritis
title_full_unstemmed Inhibition of PGE2 in Subchondral Bone Attenuates Osteoarthritis
title_short Inhibition of PGE2 in Subchondral Bone Attenuates Osteoarthritis
title_sort inhibition of pge2 in subchondral bone attenuates osteoarthritis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9454853/
https://www.ncbi.nlm.nih.gov/pubmed/36078169
http://dx.doi.org/10.3390/cells11172760
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