Reduced Frizzled-Related Protein B Expression Is Associated With Wnt/β-Catenin Signaling Activation and Calcification in Degenerative Menisci.

Authors

Yusuke Inoue, Ken Kumagai, Jisun Kim, Kimi Ishikawa, Hyonmin Choe, Hiroyuki Ike, Naomi Kobayashi, Yutaka Inaba

Published in

Journal of orthopaedic research : official publication of the Orthopaedic Research Society. Volume 44. Issue 10. Pages e70295.

Abstract

Meniscal calcification is increasingly recognized as a pathological feature associated with the progression of osteoarthritis (OA). However, the molecular mechanisms underlying this process remain poorly understood. This study aimed to investigate the involvement of Wnt/β-catenin signaling and its extracellular antagonist frizzled-related protein B (FRZB) in pathological calcification of degenerative human menisci. Human meniscal specimens were obtained from patients with knee OA and non-OA controls and analyzed histologically and immunohistochemically for calcification and expression of hypertrophic/calcification-associated markers, β-catenin, and FRZB. An in vitro calcification model using primary human meniscal cells was established, and the role of FRZB was examined by supplementation with recombinant FRZB or shRNA-mediated FRZB knockdown. Calcification was assessed with Alizarin Red S staining, and expression of Wnt/β-catenin signaling-related and hypertrophic/calcification-associated genes was analyzed using quantitative PCR and western blotting. Degenerative menisci exhibited prominent calcium deposition accompanied by increased expressions of RUNX2, collagen type X, and MMP-13. Calcified menisci showed enhanced β-catenin expression and reduced FRZB expression compared with non-calcified menisci. In an in vitro model, meniscal cell calcification was accompanied by downregulation of FRZB and activation of Wnt/β-catenin signaling, along with upregulation of RUNX2, collagen type X, and MMP-13. Recombinant FRZB attenuated Wnt/β-catenin signaling activity and reduced calcification, whereas FRZB knockdown enhanced Wnt/β-catenin signaling and increased calcium deposition. Reduced FRZB expression was associated with enhanced Wnt/β-catenin signaling activity and increased calcification in degenerative menisci. The findings suggest a potential inhibitory role for FRZB in the context of Wnt/β-catenin signaling associated meniscal calcification.

PMID:
42844706
Bibliographic data and abstract were imported from PubMed on 08 Oct 2026.

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