Alteration in cartilage matrix stiffness as an indicator and modulator of osteoarthritis

Abstract

Osteoarthritis (OA) is characterized by cartilage degeneration and destruction, leading to joint ankylosis and disability. The major challenge in diagnosing OA at early stage is not only lack of clinical symptoms but also the insufficient histological and immunohistochemical signs. Alteration in cartilage stiffness during OA progression, especially at OA initiation, has been confirmed by growing evidences. Moreover, the stiffness of cartilage extracellular matrix (ECM), pericellular matrix (PCM) and chondrocytes during OA development are dynamically changed in unique and distinct fashions, revealing possibly inconsistent conclusions when detecting cartilage matrix stiffness at different locations and scales. In addition, it will be discussed regarding the mechanisms through which OA-related cartilage degenerations exhibit stiffened or softened matrix, highlighting some critical events that generally incurred to cartilage stiffness alteration, as well as some typical molecules that participated in constituting the mechanical properties of cartilage. Finally, in vitro culturing chondrocytes in various stiffness-tunable scaffolds provided a reliable method to explore the matrix stiffness-dependent modulation of chondrocyte metabolism, which offers valuable information on optimizing implant scaffolds to maximally promote cartilage repair and regeneration during OA. Overall, this review systematically and comprehensively elucidated the current progresses in the relationship between cartilage stiffness alteration and OA progression. We hope that deeper attention and understanding in this researching field will not only develop more innovative methods in OA early detection and diagnose, but also provide promising ideas in OA therapy and prognosis.

Cartilage responses to inflammatory stimuli and adipose stem/stromal cell-derived conditioned medium: Results from an ex vivo model

“…To gain a more comprehensive understanding of the effects of inflammatory cytokines and ASC secretome on cartilage health, we plan to extend the experimental time points and capture both molecular and histological changes. The collection of preserved human cartilage represents a significant advantage considering that most used in vitro models are not representative of pivotal ECM properties, such as stiffness [ 24 ] and species-specific cellularity [ 25 ]. Nonetheless, caution is needed with severely OA-affected specimens, as heightened inflammation and tissue damage may be detected even without exogenously added cytokines.…”