The synergistic treatment of cyclolinopeptide J and calcium carbonate nanoparticles for osteoporosis via BMP/Wnt signaling: In vivo and in vitro.

The possible signaling pathways for the synergistic osteogenic differentiation of the cells induced by JCA. The JCA likely induces the osteogenesis of the cells by the Wnt/β-catenin, BMP2/Smad, and the MAPK signaling pathway. Wnt: Secreted glycoproteins; GSK-3β: Glycogen synthase kinase 3β; β-catenin: key nuclear effector of canonical Wnt signaling in the nucleus; RUNX2: Transcription factors; TCF: transcription factors; BMP2: Bone morphogenetic Protein 2; SMAD: Mothers against decapentaplegic homolog; FGF: Fibroblast growth factor; RAF: Protein kinases; MEK: Mitogen-activated protein kinase. MAPK: Microtubule-associated protein kinase. [Display omitted] • A novel bioactive Clolinopeptide J (CLJ) showed an osteogenic effect for osteoprosis. • A porous calcium carbonate (CA) was fabricated with an excellent loading capacity of CLJ. • Nanoparticles presented an synergistic effect of CLJ and CA on stimulating osteogenesis. • Nanoparticles demonstrated the best effect on osteoporosis in the OVX mice model. This research focuses on the investigation of cyclolinopeptide J (CLJ), a bioactive peptide naturally present in flaxseed, which loaded in porous calcium carbonate (CA) nanoparticles (JCA) to augment the effectiveness of CLJ on osteogenesis. The JCA was successfully synthesized with a high loading capacity (47.8 %) and encapsulation efficiency (95.6 %). Results showed that CLJ exerted an excellent osteogenic effect at 10 µM in MC3T3-E1 cells. CLJ and CA have been shown to activate osteogenic factors by modulating the Wnt/β-catenin and BMP/Smad signaling pathways. Furthermore, JCA treatment exhibited a remarkable ability to restore the intricate trabecular characteristics of bone in OVX-induced mice. The trabecular bone architecture observed in JCA-treated mice closely resembled that of healthy controls, indicating a substantial amelioration of osteoporotic bone loss. Our findings highlight the synergistic treatment of CLJ and CA in restoring bone integrity and structure and provide compelling evidence for the effectiveness of this novel functional supplement. [ABSTRACT FROM AUTHOR]