REVIEW article
Front. Immunol.
Sec. Inflammation
This article is part of the Research TopicInflammation, Immunity, and Cancer: New Pathways Towards Therapeutic InnovationView all 35 articles
Mitochondrial quality control modulating chondrocyte behavior and fate in knee osteoarthritis: mechanistic insights and therapeutic prospects
Provisionally accepted
- West China Hospital, Sichuan University, Chengdu, China
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Osteoarthritis (OA) is a highly prevalent and debilitating joint disorder that imposes a heavy burden on global public health due to its high incidence, prevalence, and disability rate, as well as the associated substantial healthcare costs. Early intervention is critical for OA management, yet current therapeutic options are limited by suboptimal efficacy, along with concerns regarding prosthetic lifespan and function in surgical treatment. While the complete etiology of OA remains elusive, cartilage degeneration is widely recognized as a core pathological feature of OA. A major barrier to optimizing OA therapeutic strategies is the lack of comprehensive insights into the underlying molecular mechanisms governing disease progression. Chondrocyte behavior and fate determination are pivotal to the onset and progression of OA: OA chondrocytes exhibit an imbalanced synthetic/catabolic profile, cluster formation, and autophagy dysregulation, accompanied by phenotypic alterations including hypertrophy and senescence. Additionally, multiple forms of chondrocyte death (apoptosis, chondroptosis, necrosis, necroptosis, autophagic cell death, pyroptosis, and ferroptosis) are implicated in driving OA development. Mitochondrial quality control (MQC), a cellular process encompassing redox homeostasis, mitophagy, mitochondrial dynamics (fusion and fission), and mitochondrial biogenesis, is essential for maintaining mitochondrial function and cellular homeostasis. Accumulating evidence indicates that MQC is closely involved in regulating chondrocyte behavior and fate in OA, and impaired MQC function may compromise chondrocyte viability and function, thereby promoting cartilage degeneration. Elucidating the MQC-mediated pathological mechanisms underlying abnormal chondrocyte behavior and fate in OA is expected to identify novel therapeutic targets for early-stage OA, thus providing new avenues for the development of more effective preventive and therapeutic strategies for this disorder.
Keywords: Cartilage, cell behavior, cell fate, Chondrocytes, Mitochondrial quality control, Osteoarthritis
Received: 23 Jul 2025; Accepted: 04 Feb 2026.
Copyright: © 2026 Si, Li, Duan, Li, Zhang and Duan. 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: Haibo Si
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