![]() ![]() Thus, the aim of this study was to investigate the performance of pre-osteoblasts in response to C sinCPI-2, mainly focusing on cell adhesion, proliferation, and differentiation mechanisms.Ģ.1 Biological macromolecule and antibodies In sum, the osteogenic potential of the C sinCPI-2 represents a new insight into cysteine proteases inhibitors of plants and this effect needs to be better addressed. ![]() When those cells were exposed to C sinCPI-2, they showed higher alkaline phosphatase activity, mineralized nodule production and expression gene of the osteogenic markers, when compared to untreated cells. This pro-osteogenic effect was demonstrated in culture of human dental pulp cell, which is a physiological source of stem cells. The C sinCPI-2 has shown inhibiting the human cathepsins K and B, and presenting important anti-inflammatory potential and also pro-osteogenic effect. Recently, a new phytocystatin derived from Citrus sinensis (sweet orange), C sinCPI-2, was identified and recombinantly produced. The cystatin derived from rice bran can be used in the production of health-promoting bioactive peptides for functional food formulation. Cystatins derived from sugarcane reduce dental enamel erosion, inhibit the causative agent of malaria and the development of melanoma in vivo. Moreover, recombinants phytocystatins have shown potential to be used in different therapeutic approaches. Phytocystatins has also been studied in crop genetic improvement. Phytocystatins participate in the regulation of cysteine proteases during programmed cell death, leaf senescence and have been related on control of phytopathogens. The endogenous cysteine- protease inhibitors are also present in plants and they are named phytocystatins. In mammals, the major regulators of the activity of cysteine cathepsins are their own endogenous inhibitors named cystatins. For this reason, there is growth pharmaceutical interest focuse on developing the cathepsin K inhibitors to control the bone resorption, although cathepsin K inhibitors have failed in osteoporosis clinical trials. Actually, there are 11 cathepsins encoded in the human genome – B, H, L, S, C, K, O, F, V, X e W among them, cathepsin K has a key role in bone resorption and is closely related to bone diseases as osteoporosis. On the other hand, these enzymes also participate in diseases involving tissue remodeling as osteoporosis, osteoarthritis, cancer, cardiovascular diseases, apical periodontitis and other inflammatory diseases. ![]() In turn, the cathepsins degrade the proteins of the extracellular matrix as collagen, laminin, fibronectin and proteoglycans and participate of physiological processes, as tissue remodeling, turnover of the extracellular matrix, inflammation signaling, among others. In addition, we saw that the increase in ERK may be associated with activation of the differentiation profile, also observed with an increase in the B-Catenin pathway and an increase in the expression of Runx2 in the group that received the treatment with C sinCPI-2.īone constantly being in remodeling in a dynamic process requiring coupling of specialized cells and molecules, depends on the activity of proteases for breaking-down organic matrix components, such as matrix metaloproteinases (MMP) and cysteine cathepsins, mainly cathepsin K. Together our data show that in the first hours of treatment, protein in C sinCPI-2 promotes an increase in the expression of adhesion markers, which decrease after 24 h, leading to the activation of Kinase-dependent cyclines (CDKs) modulating the transition from G1 to S phases cell cycle. The aim of this study was to investigate the performance of pre-osteoblasts in response to C sinCPI-2, mainly focusing on cell adhesion, proliferation and differentiation mechanisms. The osteogenic potential of the C sinCPI-2 protein represents a new insight into plants cysteine proteases inhibitors and this effect needs to be better addressed. Recently, a new phytocystatin derived from sweet orange, C sinCPI-2, has been shown to inhibit the enzymatic activity of human cathepsins, presenting anti-inflammatory potential and pro-osteogenic effect in human dental pulp cells. They are involved in initial germination rates and in plant defense mechanisms against phytopathogens. Phytocystatins are endogenous cysteine-protease inhibitors present in plants. ![]()
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