Moderate exercise mobilizes Prg4+ cells in the superficial zone of articular cartilage and maintains cartilage homeostasis

Different exercise intensities exert distinct effects on the knee joint. Overuse of the knee joint may lead to the early onset of osteoarthritis (OA), which is usually associated with injury to the superficial zone (SFZ) of articular cartilage. Proteoglycan 4 (PRG4), a representative marker of the SFZ, plays a pivotal role in articular cartilage lubrication and is mainly secreted by SFZ cells.In this study, Cre-dependent Prg4 tracing mice and wild-type mice were used, and all mice were subjected to treadmill running to induce forced movement. Additionally, the proliferation and pluripotency of SFZ cells were investigated, with relevant markers including Pcna, CD34, and others.As expected, the red fluorescence of Prg4 was significantly upregulated under moderate exercise but downregulated under excessive exercise. However, no significant changes were observed in proliferation- and stem cell-related markers, except for CD34 in the excessive exercise group. Furthermore, several anabolism and catabolism markers, such as Collagen 2, Aggrecan, and Mmp13, did not show significant changes during the exercise process.In summary, Prg4 expression increased under moderate exercise and slightly decreased under excessive exercise, which could provide guidance for formulating appropriate exercise patterns. Moreover, immunohistochemical analysis revealed that Caspase-3, one of the apoptosis markers, exhibited the same expression tendency as Prg4 during exercise.Collectively, this study demonstrated the expression patterns of Prg4 and other related markers under different exercise intensities, confirming that moderate exercise enhances Prg4 expression and that Prg4 maintains a relatively high level even under excessive exercise. Furthermore, Prg4 may regulate Caspase-3 expression through a specific signaling pathway.