Anti‐inflammatory, anti‐osteoclastic, and antioxidant activities of genistein protect against alveolar bone loss and periodontal tissue degradation in a mouse model of periodontitis

Abstract

Genistein, a dietary polyphenol primarily found in soy products, has beneficial effects on bone. However, the effect of genistein on inflammatory periodontal destruction has not been investigated in detail. We explored whether genistein protects against lipopolysaccharide (LPS)/ligature-induced periodontitis in mice. We also examined the effect of genistein on LPS-stimulated inflammatory and oxidative stress using RAW 264.7 macrophages and human gingival fibroblasts (hGFs). The results from μCT and histological analyses revealed that intraperitoneal injection of genistein (20 mg/kg body weight) daily for three weeks inhibited LPS-mediated alveolar bone loss and periodontal tissue degradation. The administration of genistein also inhibited osteoclast formation and the expression of inflammation-related molecules in the inflamed region of mice with periodontitis. Treatment with 30-70 μM genistein significantly prevented osteoclast differentiation in receptor activator of nuclear factor κB ligand- or LPS-stimulated macrophages by suppressing the expression of osteoclast-specific molecules. The addition of genistein led to a dose-dependent inhibition of the expression of inflammation-related molecules both in LPS-stimulated macrophages and hGFs. In addition, genistein at 50 μM protected hGFs from LPS-mediated stresses such as mitochondrial impairment and cellular ROS accumulation. However, such protection was significantly diminished by combined treatment with 25 nM bafilomycin A1, a chemical autophagy inhibitor. Collectively, our results indicate that genistein protects against inflammatory periodontal damage by regulating autophagy induction and inhibiting osteoclast activation, the production of inflammation mediators, and mitochondrial oxidative damage. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 2510-2521, 2017.

Oral supplementation with p‐coumaric acid protects mice against diabetes‐associated spontaneous destruction of periodontal tissue

“…Western blotting for the determination of protein level of Nrf2 and HO‐1 was carried out according to the methods described previously . Briefly, whole protein lysates were obtained from hPLFs and then separated by sodium dodecyl sulfate‐polyacrylamide gel electrophoresis (SDS‐PAGE) on 10% gels followed by electroblotting onto polyvinylidene difluoride membrane.…”

“…Alveolar bone loss was determined by μCT analysis as described previously. 24,25 Briefly, mice were anesthetized by intramuscular injection with a mixture of zoletil and rompun and µCT imaging was carried out by applying a SkyScan 1076 microfocus X-ray system (SkyScan ® ) with software including NRecon reconstruction ® , CTAn 1.8 ® , and CTvol. The X-ray source was set at 100 kV and 100 µA with a pixel size of 18 µm, a 1-mm filter, and a tomographic rotation of 180° (rotation step of 0.6°).…”

“…Western blotting for the determination of protein level of Nrf2 and HO-1 was carried out according to the methods described previously. [24][25][26] Briefly, whole protein lysates were obtained from . Bone loss between these two lines was indicated by black lines.…”

PDK1 is important lipid kinase for RANKL‐induced osteoclast formation and function via the regulation of the Akt‐GSK3β‐NFATc1 signaling cascade

“…Imbalances in the bone remodeling process favoring excessive osteoclasts bone resorption lead to bone destruction and is a hallmark feature of many pathological bone conditions including rheumatoid osteoarthritis, osteoporosis, periodontitis, pathological bone fractures, and aseptic loosening of prosthetic implants. [35][36][37][38] The multinucleated osteoclasts are formed through the fusion of monocytic precursor cells of the hematopoietic stem cell lineage and functions primarily in the resorption and degradation of the mineralized bone matrix. 39 The RANKL-RANK-TRAF6 signaling hub activates a myriad of downstream effector kinases and signaling networks that are essential for osteoclast formation and function.…”

Reversal of Epithelial–Mesenchymal Transition by Natural Anti-Inflammatory and Pro-Resolving Lipids

“…Genistein first isolated from Genista tinctoria can suppress psoriasis-related inflammation through a STAT3/NF-κB-dependent mechanism in keratinocytes [172,173]. For more detailed information about genistein's anti-inflammatory action or anti-EMT, please refer to a previous review by Spagnulo et al and Lee et al [174,175].…”