Involvement of Heat Shock Protein 47 in Osteophyte Formation of Knee Joint Osteoarthritis

• DOI: 10.1016/j.ajpath.2025.03.003
• Publication Date: 2025-04-08T08:06:16Z
• Authors: Yuta Otsuka; Arepati Adili; Masahiro Momoeda; Yoshifumi Negishi; Haruka Kaneko; Chiho Yoshinaga; Yuka Kenzaki; Takako Negishi-Koga; Muneaki Ishijima; Yasunori Okada

Osteophytes contribute to the development and progression of knee osteoarthritis (OA). Although transforming growth factor-β (TGFβ) bone morphogenic protein-2 (BMP2) are known induce osteophytes, regulators osteophyte formation remain elusive. This study aimed search for molecules that modulate osteophytosis in a mouse OA model. Proteomic analysis followed by immunohistochemistry articular cartilage identified heat shock protein 47 (HSP47), molecular chaperone procollagens, as molecule selectively overexpressed fibrocartilaginous cells. The treatment TGFβ3 BMP2 three-dimensional (3D) pellet culture mesenchymal stem cells (MSCs) caused their differentiation into osteophyte-like accompanied with upregulation HSP47. sizes stimulated 3D-cultured MSCs were significantly reduced knockdown HSP47 or AK778 (HSP47 inhibitor), due increased apoptosis. Furthermore, intraarticular injections suppressed Importantly, studies human samples demonstrated overexpression joints. Similarly, was observed BMP2-treated osteophytic cell spheroids well size reduction treatment. These findings highlight promoting function joints suggest therapeutic interventions targeting may be clinical value.