Lin Liu

Healthy limb joints are important for maintaining health and attaining longevity. Endochondral ossification (the replacement of cartilage with bone, occurring during skeletal development) is essential for bone formation, especially in long-axis bones. In contrast to endochondral ossification, chondrocyte populations in articular cartilage persist and maintain joint tissue into adulthood. Articular cartilage, a connective tissue consisting of chondrocytes and their surrounding extracellular matrices, plays an essential role in the mechanical cushioning of joints in postnatal locomotion. Osteoarthritis (OA) pathology relates to disruptions in the balance between anabolic and catabolic signals, that is, the loss of chondrocyte homeostasis due to aging or overuse of cartilages. The onset of OA increases with age, shortening a person’s healthy life expectancy. Although many people with OA experience pain, the mainstay of treatment is symptomatic therapy, and no fundamental treatment has yet been established. To establish regenerative or preventative therapies for cartilage diseases, further understanding of the mechanisms of cartilage development, morphosis, and homeostasis is required. In this review, we describe the general development of cartilage and OA pathology, followed by a discussion on anabolic and catabolic signals in cartilage homeostasis, mainly microRNAs.

Significance: Skeletal muscle atrophy occurs as a result of a variety of conditions including aging, disuse, and cachexia. In this study, we show that the transcription factor KLF5 is transiently up-regulated by metabolic and disuse stimulations and plays a pivotal role in the onset of muscle atrophy in vitro and in vivo. KLF5 physically interacts with Foxo1, and together, they regulate the transcription ofFbxo32, a key atrophy-inducing ubiquitin ligase. A synthetic retinoid, Am80, attenuates muscle atrophy in vitro and in vivo. Moreover, publicly available data sets showed that in humans,KLF5expression significantly increased with aging and with sarcopenia and correlated positively with expression of the ubiquitin ligase genesFBXO32andTRIM63.