Molecular biology reportsJul 18, 2026

How Exercise May Influence a Key Protein That Affects Joint Health in Osteoarthritis

Longevity & Aging Weekly Brief ↗PubMed ↗DOI ↗

Updated Jul 19, 2026

Abstract

Osteoarthritis (OA) is the most prevalent degenerative joint disorder worldwide, characterized by cartilage deterioration and mitochondrial dysfunction.

Mitofusin 2 (MFN2) plays a dual role in osteoarthritis, being protective in healthy conditions but potentially harmful when its function is disrupted.
Exercise may influence MFN2 expression through mechanisms like mitochondrial biogenesis and anti-inflammatory signaling.
Current evidence primarily comes from preclinical studies, suggesting a link between exercise and mitochondrial health in OA.
A model is proposed where exercise regulates MFN2, which could contribute to protecting joint cartilage.
The causal relationship between exercise and MFN2's role in osteoarthritis has yet to be validated through targeted studies.

Simplified

Osteoarthritis (OA) is currently the most prevalent degenerative joint disorder worldwide, with hallmarks including cartilage deterioration, low-grade inflammation, and mitochondrial dysfunction. In spite of intensive studies conducted in decades, there is still no disease-modifying treatment available. Mitofusin 2 (MFN2), one of the major mitochondrial fusion regulators, was recently identified as a pivotal molecular interface between mitochondria dynamics and chondrocyte differentiation in osteoarthritic joints. MFN2 demonstrates contradictory functions in the development of OA: protective in the physiological state and pathological when its function is deregulated. Safe, economic, and non-pharmacologic approach, exercise is capable of altering MFN2 expression via various mechanisms including AMPK/PGC-1α-mediated mitochondrial biogenesis, mitophagy due to mechanical loading, and anti-inflammatory NF-κB signaling. This review synthesizes current evidence, primarily from preclinical studies, suggesting that MFN2 may be a key molecular hub linking exercise to mitochondrial homeostasis in OA. We propose a testable model wherein exercise regulates MFN2 expression and function, potentially contributing to chondroprotection. However, we emphasize that the causal relationship remains to be established through targeted validation studies.

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Competing interests

No competing interests reported.

PubMed

How Exercise May Influence a Key Protein That Affects Joint Health in Osteoarthritis

Abstract

Full Text

Funding

Competing interests

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