Tiansheng Zheng

In this study, the therapeutic efficacy of Xanthohumol (XH) was evaluated as a preventive agent for extracellular matrix (ECM) degradation in osteoarthritis, using the in vivo monosodium iodoacetate-induced arthritis model in rats, along with the in vitro model of interleukin (IL)-1β-stimulated C28/I2 chondrocytes. With established concentrations of XH, the extent to which this compound may modulate cartilaginous architecture, enzymatic activity, or ECM synthesis was determined. The results clearly show that, in comparison with controls, this drug significantly reduced the catabolism of ECM, exerting a concentration-dependent effect that reduced the production of MMP13 (by 46% in vitro) with enhanced transcriptional production of collagen II (by 38% in vitro) versus controls, as well as exhibiting a cartilage degradation reduction of 31% compared with controls. The results, based on downstream messenger studies, show that this drug reduced transcriptional activation of ER-stress-driven catabolism associated with the PERK/ATF4/C/CEBPβ pathway, with a subsequent, noteworthy increase (by 52%) in the transcriptional activity of Nrf2. Over-expression or activation studies reduced the chondroprotective effects, entirely eliminating the silencing studies of Nrf2. These results clearly indicate that this drug, with its chondroprotective effects, suppresses catabolism, stimulates cartilaginous reinstatement, and reversibly decreases OARSI scores in treated animals. This study indicates that this drug may offer a promising therapeutic modality in modulating ER-stress-driven catabolysis as its pathomechanistic principle in targeted use for osteoarthritis prevention.

Endoplasmic reticulum (ER) is an important player in various intracellular signaling pathways that regulate cellular functions in many diseases. Intervertebral disc degeneration (IDD), an age-related degenerative disease, is one of the main clinical causes of low back pain. Although the pathological development of IDD is far from being fully elucidated, many studies have been shown that ER stress (ERS) is involved in IDD development and regulates various processes, such as inflammation, cellular senescence and apoptosis, excessive mechanical loading, metabolic disturbances, oxidative stress, calcium homeostasis imbalance, and extracellular matrix (ECM) dysregulation. This review summarizes the formation of ERS and the potential link between ERS and IDD development. ERS can be a promising new therapeutic target for the clinical management of IDD.

Osteoarthritis (OA) is an age-related chronic progressive degenerative disease that induces persistent pain and disabilities. The development of OA is a complex process, and the risk factors are various, including aging, genetics, trauma and altered biomechanics. Inflammation and immunity play an important role in the pathogenesis of OA. JAK/STAT pathway is one of the most prominent intracellular signaling pathways, regulating cell proliferation, differentiation, and apoptosis. Inflammatory factors can act as the initiators of JAK/STAT pathway, which is implicated in the pathophysiological activity of chondrocyte. In this article, we provide a review on the importance of JAK/STAT pathway in the pathological development of OA. Potentially, JAK/STAT pathway becomes a therapeutic target for managing OA.

Hyperglycemia-associated advanced glycation end products (AGEs) and the receptor for AGE (RAGE) contribute to nonalcoholic fatty liver disease (NAFLD). Xanthohumol (XH) exhibits protective activiti...