The SDF-1α/CXCR4 axis regulates chondrocyte mitochondrial dynamics via the ERK/AMPKα pathway

Mitochondrial quality control is crucial for maintaining chondrocyte homeostasis, and mitochondrial dysfunction is a key contributor to osteoarthritic (OA) pathogenesis. Reports have indicated that the level of SDF-1α increases during the progression of OA; however, its effects on mitochondrial dynamics in chondrocytes remain poorly understood. This study investigated the effects of SDF-1α on mitochondrial changes and its underlying molecular mechanisms. We found that SDF-1α reduced the number of mitochondria, caused the generation of many granular mitochondria via mitochondrial dynamics, and resulted in enhanced mitophagy in chondrocytes. SDF-1α activated AMPKα signalling and promoted its nuclear translocation to achieve these changes in mitochondria. Moreover, SDF-1α-induced mitochondrial changes require the participation of the receptor CXCR4, and the SDF-1α/CXCR4 regulatory axis increases cytoplasmic MAPK/ERK signalling to promote AMPKα-controlled mitochondrial changes. This study enhances our understanding of the role of SDF-1α in mitochondrial changes in chondrocytes and suggests the potential of therapeutic strategies for OA by targeting mitochondrial function.