Gram-positive bacteria cell wall-derived lipoteichoic acid induces inflammatory alveolar bone loss through prostaglandin E production in osteoblasts

Abstract

Periodontitis is an inflammatory disease associated with severe alveolar bone loss and is dominantly induced by lipopolysaccharide from Gram-negative bacteria; however, the role of Gram-positive bacteria in periodontal bone resorption remains unclear. In this study, we examined the effects of lipoteichoic acid (LTA), a major cell-wall factor of Gram-positive bacteria, on the progression of inflammatory alveolar bone loss in a model of periodontitis. In coculture of mouse primary osteoblasts and bone marrow cells, LTA induced osteoclast differentiation in a dose-dependent manner. LTA enhanced the production of PGE2 accompanying the upregulation of the mRNA expression of mPGES-1, COX-2 and RANKL in osteoblasts. The addition of indomethacin effectively blocked the LTA-induced osteoclast differentiation by suppressing the production of PGE2. Using ex vivo organ cultures of mouse alveolar bone, we found that LTA induced alveolar bone resorption and that this was suppressed by indomethacin. In an experimental model of periodontitis, LTA was locally injected into the mouse lower gingiva, and we clearly detected alveolar bone destruction using 3D-μCT. We herein demonstrate a new concept indicating that Gram-positive bacteria in addition to Gram-negative bacteria are associated with the progression of periodontal bone loss.

Mechanisms of bone remodeling and therapeutic strategies in chronic apical periodontitis

“…In addition, endotoxins in the cell wall of Gram-negative bacteria, namely LPS, can cause local tissue swelling and bone absorption, mobilize the immune response, and aggravate tissue damage, and its content is positively correlated with the degree of bone damage. LPS is a TLR4 ligand (Tominari et al, 2021), which stimulates receptor activator of nuclear factor kB ligand (RANKL) expression through TLR4 signaling. In contrast to LPS, LTA is a major constituent of the cell walls of many Gram-positive bacteria.…”

“…In contrast to LPS, LTA is a major constituent of the cell walls of many Gram-positive bacteria. LTA induces osteoclast differentiation and bone resorption and is involved in maintaining the survival of mature osteoclasts, thereby jointly causing inflammatory alveolar bone loss (Tominari et al, 2021). LTA can also stimulate the production of prostaglandin E2 (PGE2) by upregulating genes related to PGE2 synthesis in osteoblasts and participating in subsequent inflammatory responses (Tominari et al, 2021).…”

Gellan Gum-Based Bilayer Mucoadhesive Films Loaded with Moxifloxacin Hydrochloride and Clove Oil for Possible Treatment of Periodontitis

“…3 It has recently been established that Gram-negative and Gram-positive bacteria are associated with the progression of periodontal bone loss. 4 For the treatment of periodontal disease, various strategies have been developed including conventional procedures, scaling, and root planning; however these procedures are highly dependent upon clinician's skill and have an inability to reach into deep pockets or furcation areas. 5 Similarly in systemic antimicrobial therapy, maintenance of effective concentration at the required site is difficult and long-term therapy often leads to microbial resistance.…”

Immunomodulatory effects of mixed Lactobacillus plantarum on lipopolysaccharide-induced intestinal injury in mice

“…56 LPS is a significant cell wall component in Gram-negative bacteria; it acts on cell membrane receptors, activates intracellular signal transduction systems, and releases various inflammatory factors to damage the intestinal mucosal barrier. 57 In this study, compared with the control group, the levels of pro-inflammatory factors such as TNF-α, IL-6, and IL-12 were significantly increased ( P < 0.05), and the levels of anti-inflammatory factors (IL-4) were significantly reduced ( P < 0.05). The inflammatory factor levels, including TNF-α, IL-6, and IL-12, were significantly lowered in mice pre-gavaged with L. plantarum compared to the LPS group, especially in the mix group ( P < 0.05).…”