Icariin Promotes Osteogenic Differentiation in a Cell Model with NF1 Gene Knockout by Activating the cAMP/PKA/CREB Pathway

Abstract

Neurofibromatosis type 1 is a rare autosomal dominant genetic disorder, with up to 50% of patients clinically displaying skeletal defects. Currently, the pathogenesis of bone disorders in NF1 patients is unclear, and there are no effective preventive and treatment measures. In this study, we found that knockout of the NF1 gene reduced cAMP levels and osteogenic differentiation in an osteoblast model, and icariin activated the cAMP/PKA/CREB pathway to promote osteoblast differentiation of the NF1 gene knockout cell model by increasing intracellular cAMP levels. The PKA selective inhibitor H89 significantly impaired the stimulatory effect of icariin on osteogenesis in the NF1 cell model. In this study, an osteoblast model of NF1 was successfully constructed, and icariin was applied to the cell model for the first time. The results will help to elucidate the molecular mechanism of NF1 bone disease and provide new ideas for the clinical prevention and treatment of NF1 bone disease and drug development in the future.

Empowering Cartilage Restructuring with Biodegradable Magnesium Doped-Silicon Based-Nanoplatforms: Sustained Delivery and Enhanced Differentiation Potential

“…On one hand, the sustained release of Ica positively influenced chondrocyte proliferation and the secretion of proteoglycan and collagen matrix. [42][43][44] On the other hand, the Mg 2+ could potentiate the synthesis of the cartilage matrix by activation of the HIF-α pathway, 28,40 as confirmed by Figure 4G, thereby conferring a Mg 2+ -mediated improvement of cellular chondrogenic regulation. These findings suggest that both Mg and Ica combinedly contribute to the promotion of chondrogenic differentiation in BMSCs, whereas further studies are needed to investigate the cooperative impact of Mg and Ica on chondrogenic differentiation.…”