ABSTRACT
Objective@#To observe the effects of icariin (ICA) and Bu-Shen-Gu-Chi-Wan on the alveolar bone absorption of chronic periodontitis in rats, and to explore the effect and possible mechanism of ICA in the treatment of chronic periodontitis. @*Methods@#After the establishment of the periodontitis model, the rats were divided into the periodontitis group (group P), ICA high dose group (group H), ICA low dose group (group L) and Bu-Shen-Gu-Chi-Wan treatment group (group B). Each group received treatment for one month and two months, separately, and the serum osteocalcin (OCN) level was measured. Three-dimensional reconstruction was performed after micro computed tomography (micro CT) scanning to measure the bone parameters of specific points, and the distance between the enamel cementum boundary and alveolar crest (CEJ-ABC) was recorded as alveolar bone resorption value. Tissue sections were generated to evaluate the effect of ICA on alveolar bone repair and reconstruction in rats with experimental periodontitis. @*Results@# Compared with the periodontitis group (group P), OCN levels in the serum in treatment groups (groups H, L and B) were decreased significantly (P < 0.05); the values of bone volume/tissue volume (BV/TV) and trabecular number (Tb.N) in treatment groups (groups H, L and B) were significantly higher than that in group P (P < 0.05). Compared with group P, trabecular thickness (Tb.Th) values of groups H and B significantly increased, and trabecular separation (Tb.Sp) of groups H and B significantly decreased (P < 0.05). The changing trend of parameters in group L was the same as that in group H but only after two months of administration. The difference between Tb.Sp values in groups L and P was statistically significant (P < 0.05). Compared with group P, the CEJ-ABC distance significantly reduced in group L (1 month and 2 months after administration), group H (1 month and 2 months after administration), and group B (only 2 months after administration) (P < 0.05).@*Conclusion@#ICA and Bu-Shen-Gu-Chi-Wan improve the alveolar bone resorption in an experimental model of chronic periodontitis in rats, and the mechanism may be related to the regulation of osteocalcin serum levels.
ABSTRACT
OBJECTIVE The chemokine-like receptor 1 (CMKLR1, ChemR23) is a functional receptor for chemerin, the chemerin-derived nonapeptide (C9), and the amyloid β peptide 1-42 (Aβ42). Because these peptides share little sequence homology, studies were conducted to investigate their pharmaco?logical properties and regulation at CMKLR1. METHODS Cells expressing CMKLR1 were incubated with Aβ42 before stimulation with a strong agonist, the C9 peptide. Calcium mobilization, cAMP inhibition and MAP kinase activation were measured. Intramolecular FRET were determined using CMKLR1 constructs with an ECFP attached to the C- terminus and a FlAsH binding motif embedded in the first intracellular loop (IL1). RESULTS Binding of both Aβ42 and the C9 peptide induced CMKLR1 internal?ization, but only the Aβ42-induced receptor internalization involved clathrin-coated pits. Likewise, Aβ42 but not C9 stimulated β-arrestin 2 translocation to plasma membranes. A robust Ca2+ flux was observed following C9 stimulation, whereas Aβ42 was ineffective even at micromolar concentrations. Despite its low potency in calcium mobilization assay, Aβ42 was able to alter C9 -induced Ca2+ flux in dose-dependent manner: a potentiation effect at 100 pmol·L-1 of Aβ42 was followed by a suppression at 10 nmol·L-1 and further potentiation at 1 μmol·L-1. This unusual and biphasic modulatory effect was also seen in the C9-induced ERK phosphorylation but the dose curve was opposite to that of Ca2+ flux and cAMP inhibition, suggesting a reciprocal regulatory mechanism. Intramolecular FRET assay confirmed that Aβ42 modulates CMKLR1 rather than its downstream signaling pathways. CONCLUSION These findings suggest Aβ42 as an allosteric modulator that can both positively and negatively regulate the activation state of CMKLR1 in a manner that differs from existing allosteric modulatory mechanisms.