Forkhead box C1 promotes the pathology of osteoarthritis in subchondral bone osteoblasts via the Piezo1/YAP axis.

Autor: Li Z; Department of Orthopedics, The First Affiliated Hospital of Anhui Medical University, 218 JiXi Road, Hefei 230022, Anhui, China; Anhui Province Key Laboratory of Zoonoses, Anhui Medical University, Anhui, China., Hao L; Department of Orthopedics, The First Affiliated Hospital of Anhui Medical University, 218 JiXi Road, Hefei 230022, Anhui, China; Anhui Province Key Laboratory of Zoonoses, Anhui Medical University, Anhui, China., Chen S; Department of Orthopedics, The First Affiliated Hospital of Anhui Medical University, 218 JiXi Road, Hefei 230022, Anhui, China; Anhui Province Key Laboratory of Zoonoses, Anhui Medical University, Anhui, China., Fu W; Department of Orthopedics, The First Affiliated Hospital of Anhui Medical University, 218 JiXi Road, Hefei 230022, Anhui, China; Anhui Province Key Laboratory of Zoonoses, Anhui Medical University, Anhui, China., Zhang H; Department of Orthopedics, The First Affiliated Hospital of Anhui Medical University, 218 JiXi Road, Hefei 230022, Anhui, China., Yin Z; Department of Orthopedics, The First Affiliated Hospital of Anhui Medical University, 218 JiXi Road, Hefei 230022, Anhui, China. Electronic address: yinzsahgk@163.com., Wang Y; Department of Wound Repair & Plastic and Aesthetic Surgery, The First Affiliated Hospital of Anhui Medical University, Anhui, China; Anhui Public Health Clinical Center, Anhui, China. Electronic address: wangyinzx@sina.com., Wang J; Department of Orthopedics, The First Affiliated Hospital of Anhui Medical University, 218 JiXi Road, Hefei 230022, Anhui, China. Electronic address: wangjun01@ahmu.edu.cn.
Jazyk: angličtina
Zdroj: Cellular signalling [Cell Signal] 2024 Dec; Vol. 124, pp. 111463. Date of Electronic Publication: 2024 Oct 11.
DOI: 10.1016/j.cellsig.2024.111463
Abstrakt: Subchondral bone sclerosis is a key characteristic of osteoarthritis (OA). Prior research has shown that Forkhead box C1 (FoxC1) plays a role in the synovial inflammation of OA, but its specific role in the subchondral bone of OA has not been explored. Our research revealed elevated expression levels of FoxC1 and Piezo1 in OA subchondral bone tissues. Further experiments on OA subchondral bone osteoblasts with FoxC1 or Piezo1 overexpression showed increased cell proliferation activity, expression of Yes-associated Protein 1 (YAP) and osteogenic markers, and secretion of proinflammatory factors. Mechanistically, the overexpression of FoxC1 through Piezo1 activation, in combination with downstream YAP signaling, led to increased levels of alkaline phosphatase (ALP), collagen type 1 (COL1) A1, RUNX2, Osteocalcin, matrix metalloproteinase (MMP) 3, and MMP9 expression. Notably, inhibition of Piezo1 reversed the regulatory function of FoxC1. The binding of FoxC1 to the targeted area (ATATTTATTTA, residues +612 to +622) and the activation of Piezo1 transcription were verified by the dual luciferase assays. Additionally, Reduced subchondral osteosclerosis and microangiogenesis were observed in knee joints from FoxC1-conditional knockout (CKO) and Piezo1-CKO mice, indicating reduced lesions. Collectively, our study reveals the significant involvement of FoxC1 in the pathologic process of OA subchondral bone via the Piezo1/YAP signaling pathway, potentially establishing a novel therapeutic target.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024. Published by Elsevier Inc.)
Databáze: MEDLINE
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