REVIEW article
Front. Cell Dev. Biol.
Sec. Signaling
Volume 13 - 2025 | doi: 10.3389/fcell.2025.1639430
Critical Signaling Pathways in Osteoclast Differentiation and Bone Resorption: Mechanisms and Therapeutic Implications for Periprosthetic Osteolysis Type of the Study: Review Articles
Provisionally accepted
- 1Central Hospital Affiliated to Shenyang Medical College, Shenyang, China
- 2Shenyang Institute of Hand Surgery, Shenyang, China
- 3Shengjing Hospital of China Medical University, Shenyang, China
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Bone homeostasis is dynamically regulated by the balance between osteoclast-mediated bone resorption and osteoblast-driven bone formation. Periprosthetic osteolysis (PPO), a major complication following joint arthroplasty, occurs when excessive bone resorption surpasses formation, leading to implant loosening and failure. Emerging evidence highlights the pivotal roles of the RANKL/RANK/OPG axis, nuclear factor-κB (NF-κB) signaling, and mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) cascades in osteoclast differentiation and pathological bone resorption. This review systematically explores the molecular mechanisms by which these pathways regulate osteoclastogenesis and their pathological contributions to PPO. Specifically, we analyze how wear particle-induced inflammation reprograms these signaling networks to exacerbate osteolytic activity. Furthermore, we discuss potential therapeutic strategies targeting these pathways, including pharmacological inhibitors, gene therapy, and dual-target interventions, to restore bone homeostasis. By integrating recent advances in osteoimmunology and translational research, this work provides a comprehensive framework for understanding PPO pathogenesis and developing precision therapies.
Keywords: Periprosthetic osteolysis, Bone Resorption, Signaling Pathways, Osteoclasts, RANKL/RANK/OPG, NF-κB, MAPK/ERK, therapeutic targets
Received: 02 Jun 2025; Accepted: 06 Aug 2025.
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) or licensor 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.
* Correspondence: Zeming Lei, Central Hospital Affiliated to Shenyang Medical College, Shenyang, China
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