Table 2.
Summary of microbial virulence factors involved in alveolar bone loss.
| Microbial virulence factors | Principle findings | References |
|---|---|---|
| LPS | 10-3 g/L of LPS could directly stimulate bone loss, while a tiny concentration of LPS (10-9 g/L) could indirectly promote bone loss by activating the production of bone resorptive cytokines and prostaglandins. | Paula-Silva et al., 2020; Beuscher et al., 1987; Tatakis et al., 1988 |
| LPS could inhibit differentiation and proliferation while promoting apoptosis of osteoblasts via various mechanisms. | Wilson et al., 1988; Meghji et al., 1992; Tachikake-Kuramoto et al., 2014; Albus et al., 2016; Sosroseno et al., 2009 | |
| High concentrations of P. gingivalis LPS could reduce mesenchymal stem cell proliferation and osteogenic differentiation, and have the capacity to inhibit activated T cells. | Tang et al., 2015 | |
| P. gingivalis LPS increased the expression of RANKL via TLR2 in osteoblasts. | Kassem et al., 2015 | |
| LPS of oral bacteria could stimulate Notch signaling, thus inducing IL-6 expression in macrophages. Macrophages stimulated by LPS in vitro showed increased expression of JAG1, implying that LPS and Notch signaling are involved in bone loss. | Wongchana and Palaga, 2012; Skokos and Nussenzweig, 2007; Tsao et al., 2011 | |
| P. gingivalis LPS could modulate the expression of Wnt signaling, regulating alveolar bone health. | Nanbara et al., 2012; Maekawa et al., 2017; Tang et al., 2014 | |
| CPA | CPA from serotype c (CPA-c) of A. actinomycetemcomitans inhibited osteoblast cell line proliferation through a pro-apoptotic mechanism. | Yamamoto et al., 1999 |
| Protease | Red complex pathobionts damage the epithelial tissue through the production of high protease activity which allows for the translocation of immunostimulatory molecules into tissues. | Bamford et al., 2007; Saito et al., 1997 |
| Gingipains | Gingipains of P. gingivalis cleaved and degraded OPG and increased the RANKL/OPG ratio, contributing to bone loss by inducing osteoclast formation. | Tsukasaki and Takayanagi, 2019; Yasuhara et al., 2009; Akiyama et al., 2014 |
| RagA RagB |
The expression of RagA and RagB of P. gingivalis was increased after exposure to smoking, which could facilitate the invasion of P. gingivalis to the periodontium. | Bagaitkar et al., 2009 |
| OMP29 | Surface RANKL on T cells primed with A. actinomycetemcomitans-derived OMP29 was essential for osteoclastogenesis. | Lin et al., 2011 |
| Td92 | Td92, the surface protein of T. denticola, activates NLRP3 in macrophages and induces caspase-1-dependent cell death | Jun et al., 2012 |
| Td92 induces osteoclastogenesis via prostaglandin E(2)-mediated RANKL/osteoprotegerin regulation | Kim et al., 2010 | |
| Dentilisin | T. denticola dentilisin stimulates tissue-destructive cellular processes in a TLR2/MyD88/Sp1-dependent fashion | Ganther et al., 2021 |
| FimA | The upregulation of FimA suppressed the host response to P. gingivalis by abrogating the proinflammatory response to subsequent TLR2 stimulation, and, therefore, increasing bacterial survival. | Bagaitkar et al., 2010 |
| CDT | Stimulation of CDT of A. actinomycetemcomitans caused upregulation of RANKL. | Belibasakis et al., 2005 |
| LTA | LTA of E. faecalis could increase the levels of NLRP3, caspase-1, and IL-1β, which resulted in bone loss. | Yin et al., 2020 |
LPS, lipopolysaccharide; P. gingivalis, Porphyromonas gingivalis; RANKL, receptor of nuclear factor kappa B ligand; TLR, toll-like receptor; IL, interleukin; JAG1, Jagged 1; Wnt, Wingless-integrated; CPA, capsular-like polysaccharide antigen; A. actinomycetemcomitans, Aggregatibacter actinomycetemcomitans; OPG, osteoprotegerin; Rag, Ras-related GTP-binding protein; OMP, outer membrane protein; T. denticola, Treponema denticola; NLRP3, nucleotide oligomerization domain-like receptor family pyrin domain-containing 3; FimA, fimbrilin; CDT, cytolethal distending toxin; LTA, lipoteichoic acid; E. faecalis, enterococcus faecalis; NF-κB, nuclear factor kappa B; ROS, reactive oxygen species.