Reduced free cholesterol in dental follicle cells inhibits osteogenic differentiation by inducing protein kinase C activity

Morsczeck, Christian and Reck, Anja and Reichert, Torsten E. (2025) Reduced free cholesterol in dental follicle cells inhibits osteogenic differentiation by inducing protein kinase C activity. BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 786: 152750. ISSN 0006-291X, 1090-2104

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Abstract

During the osteogenic differentiation of dental follicle cells (DFCs) the concentration of free cholesterol remains constant during differentiation. In less agreement with this result, several studies have shown that inhibition of cholesterol synthesis promotes differentiation of osteogenic progenitor cells. This study therefore investigated the effect of cholesterol synthesis inhibition on the osteogenic differentiation of DFCs. The induction of osteogenic differentiation showed a significant increase in free cholesterol concentration. Inhibition of cholesterol synthesis decreased both free cholesterol concentration and the alkaline phosphatase activity, a marker of osteogenic differentiation. However, a lower concentration of the inhibitor, which does not affect the concentration of free cholesterol, did not inhibit the activity of alkaline phosphatase (ALP). Previous studies have shown that the differentiation of DFCs is controlled by classical protein kinases C (PKC) and the induction of protein kinase B (AKT). In correlation with the reduced concentration of free cholesterol, AKT was also downregulated and the activity of classical PKCs was upregulated. Although inhibition of AKT was shown to downregulate the ALP activity, induction of AKT could not compensate for the reduced differentiation following inhibition of cholesterol. However, inhibition of PKC induced ALP-activity and suppressed the inhibitory effect of low free cholesterol concentration on the ALP activity. In conclusion, our study suggests that a reduced concentration of free cholesterol has an inhibitory effect on osteogenic differentiation through activation of PKC.

Item Type: Article
Uncontrolled Keywords: OSTEOBLASTIC DIFFERENTIATION; BONE-FORMATION; IN-VITRO; SIMVASTATIN; PATHWAY; Dental follicle cells; Osteogenic differentiation; Cholesterol; Signaling pathway
Subjects: 600 Technology > 610 Medical sciences Medicine
Divisions: Medicine > Lehrstuhl für Mund-, Kiefer- und Gesichtschirurgie
Depositing User: Dr. Gernot Deinzer
Date Deposited: 22 Sep 2026 09:55
Last Modified: 22 Sep 2026 09:55
URI: https://pred.uni-regensburg.de/id/eprint/66341

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