Increased Wnt5a/ROR2 signaling is associated with chondrogenesis in meniscal degeneration

Author:

Inoue Yusuke1ORCID,Kumagai Ken1,Ishikawa Kimi1,Kato Ikuma2,Kusaba Youhei1,Naka Takuma1,Nagashima Kiyotaka1,Choe Hyonmin1,Ike Hiroyuki1,Kobayashi Naomi3ORCID,Inaba Yutaka1

Affiliation:

1. Department of Orthopaedic Surgery and Muscloskeletal Science, Graduate School of Medicine Yokohama City University Yokohama Japan

2. Department of Molecular Pathology Yokohama City University Graduate School of Medicine Yokohama Japan

3. Department of Orthopaedic Surgery Yokohama City University Medical Center Yokohama Japan

Abstract

AbstractThe aim of the present study was to investigate the association between chondrogenic differentiation and Wnt signal expression in the degenerative process of the human meniscus. Menisci were obtained from patients with and without knee osteoarthritis (OA), and degeneration was histologically assessed using a grading system. Immunohistochemistry, real‐time polymerase chain reaction (PCR), and Western blot analysis were performed to examine the expressions of chondrogenic markers and of the components of Wnt signaling. Histological analyses showed that meniscal degeneration involved a transition from a fibroblastic to a chondrogenic phenotype with the upregulation of SOX9, collagen type II, collagen type XI, and aggrecan, which were associated with increased Wnt5a and ROR2 and decreased TCF7 expressions. OA menisci showed significantly higher expressions of Wnt5a and ROR2 and significantly lower expressions of AXIN2 and TCF7 than non‐OA menisci on real‐time PCR and Western blot analysis. These results potentially demonstrated that increased expression of Wnt5a/ROR2 signaling promoted chondrogenesis with decreased expression in downstream Wnt/β‐catenin signaling. This study provides insights into the role of Wnt signaling in the process of meniscal degeneration, shifting to a chondrogenic phenotype. The findings suggested that the increased expression of Wnt5a/ROR2 and decreased expression of the downstream target of Wnt/β‐catenin signaling are associated with chondrogenesis in meniscal degeneration.

Funder

Japan Society for the Promotion of Science

Publisher

Wiley

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