curcumin and Calcinosis

The osteogenic differentiation of human aortic valve interstitial cells (hVICs) is the key cellular mechanism of calcified aortic valve disease (CAVD). This study aimed to explore how curcumin (CCM) inhibits the osteogenic differentiation of hVICs and elucidate the molecular mechanisms involved. In this study, CCM inhibited the osteogenic differentiation of hVICs under osteogenic medium (OM) conditions by reversing the OM-induced increase in calcified nodule formation and osteogenesis-specific markers (ALP and Runx2). RNA sequencing identified 475 common differentially expressed genes with Venn diagrams of the different groups. Kyoto Encyclopedia of Genes and Genomes enrichment revealed that the CCM inhibition of hVIC osteogenic differentiation was enriched in the NF-κB, PI3K-AKT, TNF, Jak-STAT, and MAPK signaling pathways. In addition, CCM suppressed the phosphorylation of ERK, IκBα, AKT, and interfered with the translocation of P65 into the cell nucleus in hVICs under OM culture conditions. In conclusion, CCM inhibited the osteogenic differentiation of hVICs via interfering with the activation of NF-κB/AKT/ERK signaling pathways. Our findings provide novel insights into a critical role for CCM in CAVD progression and shed new light on CCM-directed therapeutics for CAVD.

Topics: Aortic Valve; Aortic Valve Stenosis; Bicuspid Aortic Valve Disease; Calcinosis; Curcumin; Heart Defects, Congenital; Heart Valve Diseases; Humans; NF-kappa B; Proto-Oncogene Proteins c-akt

Tendon calcification is a common but intractable problem leading to pain and activity limitation when injury or tendinopathy progresses into the late stage. This is because tendon stem/progenitor cells (TSPCs) can undergo aberrant osteogenic differentiation under inflammatory conditions. This study aims to investigate the effect of curcumin, a natural anti-inflammatory agent, on regulating the differentiation of TSPCs in tendon calcification. With inflammatory stimulation, TSPCs showed higher alkaline phosphatase activity and more frequent formation of mineralized nodules which were verified in the culture system; however, curcumin significantly alleviated these pathological changes. In in vivo function analysis, chitosan microsphere-encapsulated curcumin was delivered to injured sites of rat tendon ectopic calcification model. The inflammation in the tendon tissues of the curcumin group was significantly relieved. Controlled-release curcumin partially rescued tendon calcification and enhanced tendon regeneration in animal model. This study demonstrates that controlled-release curcumin can manipulate the fate decision of TSPCs, and that it promotes the tenogenesis and inhibits the osteogenesis of TSPCs in a pathological microenvironment, which provides a possible new therapeutic strategy for tendon disease.

Topics: Achilles Tendon; Animals; Calcinosis; Cell Differentiation; Curcumin; Delayed-Action Preparations; Mice; Rats; Stem Cells