Background:
Osteoarthritis is a common joint disease that causes pain, stiffness, and reduced mobility, particularly in ageing populations. Current treatments can relieve symptoms but do not restore the original cartilage, the smooth tissue that cushions joints. Surgical approaches such as microfracture aim to repair damaged cartilage by stimulating the body’s own stem cells – called mesenchymal stem cells (MSCs) – to form new tissue. However, this repair tissue is often of lower quality, meaning that improvements may not last.
Objective:
An important but often overlooked factor in recovery is rehabilitation, specifically, how and when joints are moved after surgery. Mechanical loading, such as controlled movement or weight-bearing during physiotherapy, can stimulate MSCs to form cartilage. This process partly works by activating a key biological pathway known as TGF-β signalling. At the same time, increasing evidence shows that these cells are influenced by the body’s internal 24-hour clock (circadian rhythm), which regulates many processes including tissue repair. This raises a key question: could the timing of movement during the day influence how well cartilage heals?
Methods:
To address this, we study human stem cells in the laboratory under controlled conditions that mimic rehabilitation. The cells are placed in supportive gelatine scaffolds and exposed to defined daily patterns of mechanical loading using a specialised bioreactor. Some cells are stimulated with external TGF-β as positive control, while others rely only on signals generated by mechanical loading. We then measure cartilage-like matrix production, track changes in gene activity as the cells become cartilage cells and assess how their internal biological clock responds over time.
Results:
All experimental groups contained similar numbers of healthy cells, indicating that differences are indeed due to treatment rather than cell loss. After two weeks, unstimulated cells produced the least cartilage matrix, while the TGF-β group showed the highest production. However, one mechanical loading regime – short bursts of five minutes every hour – proved particularly effective. It maximised retention of cartilage matrix components in the scaffold and achieved matrix production close to the biochemically stimulated TGF-β group. This indicates that not only movement itself, but its pattern, is crucial. Other loading schedules such as two hours in the morning or three split sessions across the day also performed well, although to a lesser extent. Both timing and frequency therefore influence cartilage formation with frequent, short loading intervals being more effective than longer, less frequent sessions. To understand why, we examined the cells’ internal clocks during the two-week process. Key “clock genes” shifted over time, with increased activity of BMAL1, a gene linked to healthy cartilage. Notably, the five-minute-per-hour regime showed the strongest activation of these clock genes. This same group also displayed increased expression of cartilage marker genes (SOX9, COL2, and ACAN). In addition, genes involved in the TGF-β pathway were more active, indicating that mechanical loading can trigger this crucial cartilage formation and repair mechanism.
Conclusion:
Overall, our findings show that cartilage regeneration depends not only on how much joints are moved, but also on when and how often. Aligning rehabilitation with the body’s natural rhythms could improve recovery after joint surgery. More broadly, the success of frequent short loading periods suggests a simple message: regularly getting up and moving throughout the day - particularly during office work may help support long-term joint health.