Effects of 5-lipoxygenase gene disruption on inflammation, osteoclastogenesis and bone resorption in polymicrobial apical periodontitis

Abstract

Objectives: To investigate the regulation of inflammatory and osteoclastogenic signaling by 5-lipoxygenase (5-LO) in apical periodontitis induced by oral contamination of dental root canals in mice.

Design: Apical periodontitis was induced in 5-lipoxygenase enzyme knockout (129-Alox5^tm1Fun) and 129 wild-type mice (n = 96) by exposure of the dental root canal to the oral cavity. After 7, 14, 21, and 28 days, the animals were euthanized and the tissues removed (n = 12 teeth per period) for histopathological and histometric analyses (hematoxylin and eosin [HE]), evaluation of osteoclastogenic activity (tartrate-resistant acid phosphatase enzyme [TRAP]), and determination of inflammatory and osteoclastogenic signaling (qRT-PCR).

Results: Oral contamination of dental root canals induced recruitment of neutrophils and osteoclasts to the periodontal ligament, resulting in bone resorption. Absence of 5-LO did not impair neutrophil recruitment while osteoclastic formation was increased. Nonetheless, early bone resorption progressed similarly to lesions in wild-type animals. Interestingly, in the absence of 5-LO, the synthesis of mRNAs for cytokines, chemokines, and their receptors was significantly reduced while that of regulators of osteoclastogenesis (RANK, RANKL, and OPG) was increased in comparison with the corresponding levels in wild-type animals.

Conclusions: The 5-LO pathway plays a role in the stimulation of inflammatory mediator synthesis and inhibition of osteoclastogenesis in apical periodontitis in mice. However, the paradoxical inflammatory-osteoclastogenic signaling did not impair inflammatory cell recruitment and bone resorption during early development of the disease.

Keywords: 5-lipoxygenase; Apical periodontitis; Bone resorption; Inflammation; Osteoclastogenesis.