Calcitriol-enhanced autophagy in gingival epithelium attenuates periodontal inflammation in rats with type 2 diabetes mellitus.
Wang. Yanan Y; Huang. Maoting M; Xu. Wanlin W; Li. Fulong F; Ma. Chunliang C; Tang. Xiaolin X
Key Findings
- Calcitriol increased autophagy markers (higher LC3‑II/LC3‑I) in gingival epithelium
- Calcitriol lowered inflammatory NF‑κB‑p65 and p62/SQSTM1 levels
- Calcitriol rescued the drop in LL‑37 levels caused by diabetes‑related periodontitis
Practical Outcomes
- The study suggests that adequate vitamin D status, or possibly calcitriol supplementation, might support gum health and antimicrobial defenses in people with type‑2 diabetes. However, the work is in rats and uses a prescription‑only form of vitamin D, so biohackers should stick to safe, over‑the‑counter vitamin D3 dosing and monitor blood levels before considering higher‑dose or active‑form supplements.
Summary
In diabetic rats with gum disease, giving the active form of vitamin D (calcitriol) boosted a cell‑clean‑up process called autophagy, lowered inflammation signals, and restored the natural antimicrobial peptide LL‑37 in gum cells, which together helped reduce periodontal damage.
Abstract
Type 2 diabetes mellitus (T2DM)-associated periodontitis is a common disease with high prevalence, associated with persistent infection and complicated manifestations. Calcitriol (1 alpha, 25-dihydroxyvitamin D3, 1,25D) is the active form of vitamin D that plays a protective role in immune regulation, bone metabolism, and inflammatory response. In this study, we constructed a T2DM model in rats by combining a high-fat diet with low-dose streptozotocin. The periodontitis model in rats was developed by ligation and <i>Porphyromonas gingivalis</i> (ATCC 33277) inoculation. Rats were randomly divided into five groups: non-diabetic blank, diabetic blank, diabetes with calcitriol treatment, diabetes with 3-methyladenine (3-MA) treatment, or diabetes with calcitriol and 3-MA treatment. The diabetic rats exhibited an intense inflammatory response and decreased autophagy compared with the non-diabetic rats. Intraperitoneal injection of calcitriol and autophagy inhibitor (3-MA) allowed us to explore the effect of calcitriol on inflammation in the gingival epithelium and the role of autophagy in this process. Treatment with calcitriol resulted in the decreased expression of NFκB-p65, p62/SQSTM1 and inflammatory response and increased expression of LC3-II/LC3-I. Application of 3-MA significantly suppressed autophagy, which was apparently retrieved by calcitriol. Antibacterial peptide (LL-37) is the only antimicrobial peptide in the cathelicidin family that is found in the human body, and it exhibits a broad spectrum of antibacterial activity and regulates the immune system. In the present study, our findings indicated that calcitriol-enhanced autophagy may attenuated periodontitis and the decrease of LL-37 was rescued by calcitriol treatment in the gingival epithelial cells of T2DM rats. Our study provides evidence for the application of calcitriol as an adjunctive treatment for T2DM-associated periodontitis.
Study Information
pubmed
2023
2023-01-10T00:00:00.000Z
10.3389/fendo.2022.1051374
11
52