Osteoblast Lineage Cells Play an Essential Role in Periodontal Bone Loss Through Activation of Nuclear Factor-Kappa B

Abstract

Bacterial pathogens stimulate periodontitis, the most common osteolytic disease in humans and the most common cause of tooth loss in adults. Previous studies identified leukocytes and their products as key factors in this process. We demonstrate for the first time that osteoblast lineage cells play a critical role in periodontal disease. Oral infection stimulated nuclear localization of NF-κB in osteoblasts and osteocytes in the periodontium of wild type but not transgenic mice that expressed a lineage specific dominant negative mutant of IKK (IKK-DN) in osteoblast lineage cells. Wild-type mice were also susceptible to bacteria induced periodontal bone loss but transgenic mice were not. The lack of bone loss in the experimental group was linked to reduced RANKL expression by osteoblast lineage cells that led to diminished osteoclast mediated bone resorption and greater coupled new bone formation. The results demonstrate that osteoblast lineage cells are key contributors to periodontal bone loss through an NF-κB mediated mechanism.

Osteocytes play an important role in experimental periodontitis in healthy and diabetic mice through expression of RANKL

“…To our knowledge, the expression of RANKL by osteocytes in humans has not been examined. We have previously shown that the introduction of periodontal pathogens to the oral cavity of mice induces NF‐kB and RANKL expression in osteoblastic bone‐lining cells and osteocytes (Pacios et al., ). Although we saw statistical differences in bone resorption and osteoclast numbers and activity between WT and experimental mice, we cannot rule out the possibility that leucocyte sources of RANKL may also play a role in periodontal bone loss.…”

“…Porphyromonas gingivalis (Pg) strain (ATCC 33277) and Fusobacterium nucleatum (Fn) strain (ATCC 25586) were inoculated in 100 μl of sterile methylcellulose so that 2 × 10 9 colony‐forming units of each bacterium were applied in 200 μl of 2% methylcellulose. Oral inoculation with Porphyromonas gingivalis–Fusobacterium nucleatum bacteria (Pg‐Fn) is an effective model for studying periodontitis (Polak et al., ) and a dose which we have previously published and found to be effective in mice with a C57/B6 background (Pacios et al., ). Bacterial inoculation was performed three times per week over a 2‐week period.…”

“…In contrast, osteoblast lineage cells are an important source of RANKL in conditions characterized by unloading of mechanical forces, bone loss induced by ovariectomy or arthritis, whereas the loss of RANKL in T lymphocytes does not confer such protection (Fumoto, Takeshita, Ito, & Ikeda, ; Nakashima et al., ; Xiong et al., ). Moreover, we have shown that the induction of periodontal disease in mice stimulates RANKL production in bone‐lining osteoblastic cells and osteocytes (Pacios et al., ). However, the specific role of osteocytes in contributing to bacteria‐induced periodontal bone loss has not been investigated.…”

Transcriptomics, NF-κB Pathway, and Their Potential Spaceflight-Related Health Consequences

“…For instance, NF-κB plays a role in osteoclastogenesis [22] and changes in osteoblast activities [23,24]. NF-κB is also suggested to play a role in muscle atrophy due to its increased expression in cardiac cell unloading [25].…”

Osteoimmunology: Inflammatory osteolysis and regeneration of the alveolar bone

“…The question arises about the main source of RANKL that pushes osteoclastogenesis during inflammatory osteolysis. The relevance of osteocytes (DMP1‐Cre) (Graves et al., ) and osteogenic lineage cells (IKK‐DN) (Pacios et al., ) in periodontal inflammatory bone loss has been already mentioned. Moreover, RANKL produced by periodontal ligament and bone‐lining cells (Col1α1‐Cre) provides the major driving force for tooth movement in response to orthodontic forces (Yang et al., ).…”