A RANKL-UCHL1-sCD13 negative feedback loop limits osteoclastogenesis in subchondral bone to prevent osteoarthritis progression.

Autor: Liang W; Department of Cell Biology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, China. liangwqycy@163.com.; Department of Anatomy, School of Basic Medical Sciences, Southern Medical University, Guangzhou, China. liangwqycy@163.com., Feng R; Department of Rehabilitation medicine, The Third Affiliated Hospital of Southern Medical University, Guangzhou, China.; School of Rehabilitation, Capital Medical University, Beijing, China.; Department of Spinal and Neural Functional Reconstruction, China Rehabilitation Research Center, Beijing, China., Li X; Department of Rehabilitation medicine, The Third Affiliated Hospital of Southern Medical University, Guangzhou, China., Duan X; Department of Cell Biology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, China., Feng S; State Key Laboratory of Biocontrol and Guangdong Provincial Key Laboratory of Plant Resources, School of Life Sciences, Sun Yat-sen University, Guangzhou, China., Chen J; Department of Rehabilitation Medicine, Nanfang Hospital of Southern Medical University, Guangzhou, China., Li Y; Department of Rehabilitation medicine, The Third Affiliated Hospital of Southern Medical University, Guangzhou, China., Chen J; Department of Rehabilitation medicine, The Third Affiliated Hospital of Southern Medical University, Guangzhou, China., Liu Z; Department of Orthopaedics, The Third Affiliated Hospital of Southern Medical University, Guangzhou, China., Wang X; Department of Orthopaedics, The Third Affiliated Hospital of Southern Medical University, Guangzhou, China., Ruan G; Clinical Research Centre, Guangzhou First People's Hospital, Guangzhou, China., Tang S; Clinical Research Centre, Zhujiang Hospital, Southern Medical University, Guangzhou, China., Ding C; Clinical Research Centre, Zhujiang Hospital, Southern Medical University, Guangzhou, China., Huang B; Department of Orthopaedics, The Third Affiliated Hospital of Southern Medical University, Guangzhou, China. binxue483@163.com., Zou Z; Department of Cell Biology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, China. zzp@smu.edu.cn., Chen T; Department of Orthopaedics, The Third Affiliated Hospital of Southern Medical University, Guangzhou, China. nysycty@163.com.; Department of Orthopaedic Surgery, Third Hospital of Hebei Medical University, Shijiazhuang, China. nysycty@163.com.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2024 Oct 10; Vol. 15 (1), pp. 8792. Date of Electronic Publication: 2024 Oct 10.
DOI: 10.1038/s41467-024-53119-2
Abstrakt: Abnormal subchondral bone remodeling plays a pivotal role in the progression of osteoarthritis (OA). Here, we analyzed subchondral bone samples from OA patients and observed a significant upregulation of ubiquitin carboxy-terminal hydrolase L1 (UCHL1) specifically in subchondral bone osteoclasts. Notably, we found a strong correlation between UCHL1 expression and osteoclast activity in the subchondral bone during OA progression in both human and murine models. Conditional UCHL1 deletion in osteoclast precursors exacerbated OA progression, while its overexpression, mediated by adeno-associated virus 9, alleviated this process in male mice. Mechanistically, RANKL stimulates UCHL1 expression in osteoclast precursors, subsequently stabilizing CD13, augmenting soluble CD13 (sCD13) release, and triggering an autocrine inhibitory effect on the MAPK pathway, thereby suppressing osteoclast formation. These findings unveil a previously unidentified negative feedback loop, RANKL-UCHL1-sCD13, that modulates osteoclast formation and presents a potential therapeutic target for OA.
(© 2024. The Author(s).)
Databáze: MEDLINE
Externí odkaz: