Abstract
ObjectivesThe objective of the present study was to investigate the effect of lipoxin-type A4 (LXA4) on bacterial-induced osteoclastogenesis.Material and methodsHuman periodontal ligament cells (PDLCs) in coculture with osteoclast precursors (RAW264.7 cells) were exposed to bacterial stimulation with lipopolysaccharide (LPS) to induce inflammation. After 24 h, cells were treated to 100 ng/ml of LXA4 and 50 ng/ml of forymul peptide receptor 2 (FPR2/ALX) receptor antagonist (Boc-2). After 5 days, osteoclastic resorptive activity was assessed on calcium phosphate (CaP) synthetic bone substitute. Additionally, osteoclastic differentiation was evaluated using tartrate-resistant acid phosphatase (TRAP) staining, TRAP enzymatic activity assay, and on the expression of osteoclast-specific genes.ResultsWe found that stimulation of in the osteoclasts with LPS-stimulated PDLCs induced a significant increase in tartrate-resistant acid phosphatase (TRAP) positive cells, higher resorptive activity, and enhanced expression of specific genes. Meanwhile, LXA4-treatment exhibited strong anti-inflammatory activity, and was able to reverse these inflammatory effects.ConclusionsWe conclude that (1) PDLCs are a potential target for treating bacterial-induced bone resorption in patients with periodontal disease, and (2) LXA4 is a suitable candidate for such therapy.Clinical relevanceThe results prove that lipoxins have a protective role in bacterial-induced periodontal inflammation and alveolar bone resorption, which can be translated into a clinical beneficial alterative treatment.
Highlights
Periodontal disease, the most common chronic disease in humans, is characterized by inflammation of the supporting tissues around the teeth [1]
Microorganisms (e.g., Porphyromonas gingivalis, Fusobacterium nucleatum, and Escherichia coli) promote the periodontal ligament cells (PDLCs) to interact with osteoclast progenitor cells (OPCs), which leads to the differentiation of these OPCs into mature osteoclasts [8, 9]
The cascade of infection, inflammation mediated by the PDLCs, and osteoclast differentiation presents an important drug target for therapeutic agents aimed at suppressing bone loss
Summary
Periodontal disease, the most common chronic disease in humans, is characterized by inflammation of the supporting tissues around the teeth [1]. Microorganisms (e.g., Porphyromonas gingivalis, Fusobacterium nucleatum, and Escherichia coli) promote the PDLCs to interact with osteoclast progenitor cells (OPCs), which leads to the differentiation of these OPCs into mature osteoclasts [8, 9] During this interaction, PDLCs attract and stimulate the differentiation of OPCs towards mature osteoclasts via expression of adhesion molecules, such as adhesion molecule-1 (ICAM-1), and expression of osteoclastogenesis stimulatory factors, such as RANKL, M-CSF, and tumor necrosis factor-alpha (TNFα) [10]. PDLCs attract and stimulate the differentiation of OPCs towards mature osteoclasts via expression of adhesion molecules, such as adhesion molecule-1 (ICAM-1), and expression of osteoclastogenesis stimulatory factors, such as RANKL, M-CSF, and tumor necrosis factor-alpha (TNFα) [10] In vivo, this leads to retraction of PDLCs and migration of OPCs to the bone surface; where the OPCs mature into bone-resorbing osteoclasts [11,12,13,14]. The cascade of infection, inflammation mediated by the PDLCs, and osteoclast differentiation presents an important drug target for therapeutic agents aimed at suppressing bone loss
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