Abstract
Osteoarthritis (OA) is an evolving disease and a major cause of pain and impaired mobility. A deeper understanding of cartilage metabolism in response to loading is critical to achieve greater insight into OA mechanisms. While physiological joint loading helps maintain cartilage integrity, reduced or excessive loading have catabolic effects. 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. In the proposed protocol, the combination of biomechanical data and medical imaging are integrated with molecular information about chondrocyte mechanotransduction and tissue homeostasis. 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. The modulation of molecules involved in cartilage homeostasis, mechanotransduction, inflammation, pain and wound healing can be analyzed in chondrocytes and culture supernatants. 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.
Highlights
Osteoarthritis (OA) is considered the sixth-leading cause of disability in the world (Kloppenburg and Berenbaum, 2020)
Among the most important factors affecting knee OA are the severity of the degenerative changes due to biomechanical factors, such as the lower limb mechanical axis and abnormal knee joint kinematics (Moschella et al, 2006)
In a recent study we demonstrated that compression of OA human cartilage modulates the inflammatory milieu by differently affecting the expression of components and homeostasis regulators of cartilage extracellular matrix (Dolzani et al, 2019)
Summary
Osteoarthritis (OA) is considered the sixth-leading cause of disability in the world (Kloppenburg and Berenbaum, 2020). Among the most important factors affecting knee OA are the severity of the degenerative changes due to biomechanical factors, such as the lower limb mechanical axis and abnormal knee joint kinematics (Moschella et al, 2006) In this perspective, a thorough in vivo biomechanical analysis to estimate the knee internal joint forces and contact areas during locomotion is essential to fully understand knee functioning (Hinterwimmer et al, 2005; Berti et al, 2006; Edwards et al, 2008; Morimoto et al, 2009; Hosseini et al, 2010; Scheys et al, 2013; Battaglia et al, 2014). In the last phase (P3), all obtained data are meant to be merged for overall comparison and final evaluations
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
