Cystatin-like protein of sweet orange (CsinCPI-2) modulates pre-osteoblast differentiation via β-Catenin involvement

Made available in DSpace on 2021-06-25T10:56:37Z (GMT). No. of bitstreams: 0 Previous issue date: 2021-04-01 Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) Phytocystatins are endogenous cysteine-protease inhibitors present in plants. They are involved in initial germination rates and in plant defense mechanisms against phytopathogens. Recently, a new phytocystatin derived from sweet orange, CsinCPI-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. The osteogenic potential of the CsinCPI-2 protein represents a new insight into plants cysteine proteases inhibitors and this effect needs to be better addressed. The aim of this study was to investigate the performance of pre-osteoblasts in response to CsinCPI-2, mainly focusing on cell adhesion, proliferation and differentiation mechanisms. Together our data show that in the first hours of treatment, protein in CsinCPI-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. 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 CsinCPI-2. [Figure not available: see fulltext.]. Department of Chemistry and Biochemistry Laboratory of Bioassays and Cell Dynamics Institute of Biosciences Sao Paulo State University – UNESP Department of Restorative Dentistry School of Dentistry at Araraquara Sao Paulo State University – UNESP Department of Genetic and Evolution Federal University of Sao Carlos Department of Diagnosis and Surgery School of Dentistry at Araraquara Sao Paulo State University–UNESP Department of Chemistry and Biochemistry Laboratory of Bioassays and Cell Dynamics Institute of Biosciences Sao Paulo State University – UNESP Department of Restorative Dentistry School of Dentistry at Araraquara Sao Paulo State University – UNESP Department of Diagnosis and Surgery School of Dentistry at Araraquara Sao Paulo State University–UNESP FAPESP: 2012/24278-5