While walking and exercise therapy are considered effective for pain relief ( Huang et al., 2003 Beckwee et al., 2013 Juhl et al., 2014 Fransen et al., 2015) and are generally recommended ( Fernandes et al., 2013 Bruyere et al., 2014 McAlindon et al., 2014 Nelson et al., 2014), most patients suffering from severe OA will eventually need surgical treatments. In particular, knee OA was ranked the 11th highest contributor to global disability showing a global age-standardized prevalence of 3.8% ( Cross et al., 2014). Weight-bearing joints, such as the hip and knee, are the most affected anatomical structures. In particular, worldwide estimates report that 9.6% of male and 18% of females aged above 60 years show symptomatic OA ( Woolf and Pfleger, 2003 World Health Organization, 2003). Since OA is non-reversible, its prevalence increases significantly with age, although with differences between genders. It is an evolving disease and a major cause of impaired mobility leading to an important reduction of the quality of life and increased costs on healthcare systems ( World Health Organization, 2003 Piscitelli et al., 2012). Osteoarthritis (OA) is considered the sixth-leading cause of disability in the world ( Kloppenburg and Berenbaum, 2020). A thorough analysis performed with the proposed methodology, combining in vivo functional biomechanical evaluations with ex vivo molecular assessments is expected to provide new insights on the beneficial effects of physiological loading and contribute to the design and optimization of non-pharmacological treatments limiting OA progression. The modulation of molecules involved in cartilage homeostasis, mechanotransduction, inflammation, pain and wound healing can be analyzed in chondrocytes and culture supernatants. The protocol appears to be flexible and suitable to analyze human OA knee cartilage explants, with different degrees of degeneration, undergoing ex vivo realistic cyclic joint loading estimated via gait analysis in patients simulating mild activities of daily living. In the proposed protocol, the combination of biomechanical data and medical imaging are integrated with molecular information about chondrocyte mechanotransduction and tissue homeostasis. The main scope of this study is to present an original methodology potentially capable to elucidate the effect of cyclic joint loading on cartilage metabolism, to identify mechanisms involved in preventing or slowing down OA progression, and to provide preliminary data on its application. While physiological joint loading helps maintain cartilage integrity, reduced or excessive loading have catabolic effects.

A deeper understanding of cartilage metabolism in response to loading is critical to achieve greater insight into OA mechanisms. Osteoarthritis (OA) is an evolving disease and a major cause of pain and impaired mobility.

Millumin spline movement