Aortic valve calcification disease (CAVD) is the most prevalent degenerative valve disease in humans, leading to significant morbidity and mortality. Despite its common occurrence, our understanding of the underlying mechanisms remains incomplete, and available treatment options are limited and risky. A more comprehensive understanding of the biology of CAVD is essential to identify new therapeutic strategies. Animal models have played a crucial role in advancing our knowledge of CAVD and exploring potential treatments. However, these models have inherent limitations as they cannot fully replicate the complex physiological mechanisms of human CAVD. In this review, we examine various CAVD models ranging from pigs to mice, highlighting the unique characteristics of each model to enhance our understanding of CAVD. While these models offer valuable insights, they also have limitations and shortcomings. We propose that the guide wire model shows promise for future CAVD research, and streamlining the methodology could enhance our understanding and expand the research scope in this field.
Tendon calcification is a common clinical condition that frequently occurs as a complication after tendon injury and surgery,or as an expression of fibrodysplasia ossificans progressiva.This condition can be referred to by various names in clinical practice and literature,including tendon ossification,tendon mineralization,heterotopic ossification,and calcific tendonitis.The exact pathogenesis of tendon calcification remains uncertain,but current mainstream research suggests that calcification is mostly cell mediated.To further elucidate the pathogenesis of tendon calcification and to better simulate the overall process,selecting appropriate experimental animal models is important.Numerous animal models have been utilized in various clinical studies,each with its own set of advantages and limitations.In this review,we have discussed the advancements made in research on animal models of tendon calcification,with a focus on the selection of experimental animals,the sites of injury in these models,and the methods employed for modeling.
Ruichen LiCanhao LaiHong LuoYujian LanXinfang DuanDingsu BaoZhipeng HouHuan LiuShijie Fu
Calcification of cartilage by hydroxyapatite is a hallmark of osteoarthritis and its deposition strongly correlates with the severity of osteoarthritis.However,no effective strategies are available to date on the prevention of hydroxyapatite deposition within the osteoarthritic cartilage and its role in the pathogenesis of this degenerative condition is still controversial.Therefore,the present work aims at uncovering the pathogenic mechanism of intra-cartilaginous hydroxyapatite in osteoarthritis and developing feasible strategies to counter its detrimental effects.With the use of in vitro and in vivo models of osteoarthritis,hydroxyapatite crystallites deposited in the cartilage are found to be phagocytized by resident chondrocytes and processed by the lysosomes of those cells.This results in lysosomal membrane permeabilization(LMP)and release of cathepsin B(CTSB)into the cytosol.The cytosolic CTSB,in turn,activates NOD-like receptor protein-3(NLRP3)inflammasomes and subsequently instigates chondrocyte pyroptosis.Inhibition of LMP and CTSB in vivo are effective in managing the progression of osteoarthritis.The present work provides a conceptual therapeutic solution for the prevention of osteoarthritis via alleviation of lysosomal destabilization.
Siliceous diatoms are one of the most prominent actors in the oceans,and they account for approximately 40%of the primary production and particulate organic carbon export flux.It is believed that changes in carbon flux caused by variations in diatom distribution can lead to significant climate shifts.Although the fundamental pathways of diatom-driven carbon sequestration have long been established,there are no reports of CaCO_(3) precipitation induced by marine diatom species.This manuscript introduces novel details regarding the enhancement of aragonite precipitation during photosynthesis in Skeletonema costatum in both artificial and natural seawater.Through direct measurements of cell surfaces via a pH microelectrode and zeta potential analyzer,it was determined that the diatom-mediated promotion of CaCO_(3) precipitation is achieved through the creation of specific microenvironments with concentrated[CO_(3)^(2-)]and[Ca^(2+)]and/or the dehydrating effect of adsorbed Ca^(2+).Based on this mechanism,it is highly plausible that diatom-mediated calcification could occur in the oceans,an assertion that was supported by the significant deviation of total alkalinity(TA)from the conservative TA-salinity mixing line during a Skeletonema costatum bloom in the East China Sea and other similar occurrences.The newly discovered calcification pathway establishes a link between particulate inorganic and organic carbon flux and thus helps in the reassessment of marine carbon export fluxes and CO_(2) sequestration efficiency.This discovery may have important ramifications for assessing marine carbon cycling and predicting the potential effects of future ocean acidification.
