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. 2025 Aug 26;13:1639430. doi: 10.3389/fcell.2025.1639430

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Copyright © 2025 Yin, Sun, Zhang, Li, Wang, Bai and Lei.

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

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The diagram illustrates the molecular pathway involving macrophages, fibroblasts, and osteoclasts. It shows CD40, TLR, IL-1R, and TNFR receptors on a macrophage leading to pathways involving NIK, IKK, and NEMO. The degradation of IκBα releases RelA and P50 into the nucleus, resulting in the transcription of TNF-α, IL-1, IL-6, MCP-1, and RANKL. These molecules stimulate fibroblasts, causing tissue destruction, and activate osteoclasts, leading to osteolysis through the expression of TRAP, CTSK, and other enzymes. — NF-κB activation and therapeutic modulation in periprosthetic osteolysis.