Porphyromonas gingivalis infection increases osteoclastic bone resorption and osteoblastic bone formation in a periodontitis mouse model

Abstract

BackgroundPorphyromonas gingivalis has been shown to invade osteoblasts and inhibit their differentiation and mineralization in vitro. However, it is unclear if P. gingivalis can invade osteoblasts in vivo and how this would affect alveolar osteoblast/osteoclast dynamics. This study aims to answer these questions using a periodontitis mouse model under repetitive P. gingivalis inoculations.MethodsFor 3-month-old BALB/cByJ female mice, 109 CFU of P. gingivalis were inoculated onto the gingival margin of maxillary molars 4 times at 2-day intervals. After 2 weeks, another 4 inoculations at 2-day intervals were applied. Calcein was injected 7 and 2 days before sacrificing animals to label the newly formed bone. Four weeks after final inoculation, mice were sacrificed and maxilla collected. Immunohistochemistry, micro-CT, and bone histomorphometry were performed on the specimens. Sham infection with only vehicle was the control.ResultsP. gingivalis was found to invade gingival epithelia, periodontal ligament fibroblasts, and alveolar osteoblasts. Micro-CT showed alveolar bone resorption and significant reduction of bone mineral density and content in the infected mice compared to the controls. Bone histomorphometry showed a decrease in osteoblasts, an increase in osteoclasts and bone resorption, and a surprisingly increased osteoblastic bone formation in the infected mice compared to the controls.ConclusionsP. gingivalis invades alveolar osteoblasts in the periodontitis mouse model and cause alveolar bone loss. Although P. gingivalis appears to suppress osteoblast pool and enhance osteoclastic bone resorption, the bone formation capacity is temporarily elevated in the infected mice, possibly via some anti-microbial compensational mechanisms.

Enhanced Activity of the Macrophage M1/M2 Phenotypes and Phenotypic Switch to M1 in Periodontal Infection

“…Alveolar bone was scanned using a micro‐CT system # at an 8‐μm resolution, followed by reconstruction of the micro‐CT images. The volume of interest was delineated on the axial planes between the mesial root surface of the first molar and the distal root surface of the third molar 18 , 19 . The contours were delineated continuously every five data planes from the furcation roof to the root apex until a three‐dimensional volume of interest was generated 18 , 19 .…”

“…The volume of interest was delineated on the axial planes between the mesial root surface of the first molar and the distal root surface of the third molar 18 , 19 . The contours were delineated continuously every five data planes from the furcation roof to the root apex until a three‐dimensional volume of interest was generated 18 , 19 . The total volume was calculated by excluding the root volume from the volume of interest 18 , 19 .…”

“…The contours were delineated continuously every five data planes from the furcation roof to the root apex until a three‐dimensional volume of interest was generated 18 , 19 . The total volume was calculated by excluding the root volume from the volume of interest 18 , 19 . The bone volume fraction was calculated by dividing the remaining bone volume by the volume of interest 18 , 19 .…”

“…The total volume was calculated by excluding the root volume from the volume of interest 18 , 19 . The bone volume fraction was calculated by dividing the remaining bone volume by the volume of interest 18 , 19 . After micro‐CT analysis, the alveolar bone was stained with 1% methylene blue as previously described 20 .…”

Porphyromonas gingivalis promotes the cell cycle and inflammatory cytokine production in periodontal ligament fibroblasts

“…Zhang et al observed that P. gingivalis invaded into gingival epithelial cells, periodontal ligament fibroblasts, and alveolar osteoblasts in a periodontitis mouse model. 6 Infection by P. gingivalis could modulate host immune-inflammatory responses and ultimately destroy the balance of the normal cell cycle and apoptosis, thereby leading to periodontal tissue destruction. [7][8][9] The cell cycle is the key step in cell proliferation, differentiation and senescence in multicellular tissues.…”