Parathyroid hormone attenuates osteoarthritis pain by remodeling subchondral bone in mice

• Published in: eLife Vol. 10
• Main Authors: Sun, Qi, Zhen, Gehua, Li, Tuo Peter, Guo, Qiaoyue, Li, Yusheng, Su, Weiping, Xue, Peng, Wang, Xiao, Wan, Mei, Guan, Yun, Dong, Xinzhong, Li, Shaohua, Cai, Ming, Cao, Xu
• Format: Journal Article
• Language: English
• Published: England eLife Science Publications, Ltd 01-03-2021; eLife Sciences Publications Ltd; eLife Sciences Publications, Ltd
• Subjects: Animals; Antiarthritic agents; Arthritis; Bone and Bones - innervation; Bone and Bones - pathology; Bone marrow; Bone remodeling; Bone Remodeling - drug effects; Care and treatment; Cartilage; Cartilage (articular); Cartilage diseases; Chronic pain; Comparative analysis; Degeneration; Dinoprostone; Disease Models, Animal; Drug approval; Edema; Endocytosis; Gait; Hindlimb; Hormones; Innervation; Knee; Male; Medicine; Meniscus; Meniscus - injuries; Mesenchyme; Mice; Mice, Inbred C57BL; Mice, Transgenic; Nestin; Osteoarthritis; Osteoarthritis - drug therapy; Pain; Pain - drug therapy; Parathyroid; Parathyroid hormone; Parathyroid Hormone - administration & dosage; Parathyroid Hormone - pharmacology; Prostaglandin E2; Prostaglandins E; Quantitative analysis; Stem cells; Stromal cells; Subchondral bone; Surgery; Transforming growth factor-b; United States > US; mouse; parathyroid hormone; subchondral bone; pain; medicine; osteoarthritis
• ISSN: 2050-084X; 2050-084X
• DOI: 10.7554/eLife.66532

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.